rs55701254

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4BA1BP7

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency (the lower threshold of the 95% CI of 1456/25104) of the c.1708-18T>A variant in the SLC26A4 gene is 5.55% for European (Finnish) chromosomes by gnomAD v2.1.1, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). This silent variant in SLC26A4 is not predicted by the computational prediction analysis using MaxEntScan to impact splicing (BP7, BP4). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BA1, BP7, BP4. LINK:https://erepo.genome.network/evrepo/ui/classification/CA4432923/MONDO:0010134/005

Frequency

Genomes: 𝑓 0.024 ( 74 hom., cov: 32)

Exomes 𝑓: 0.030 ( 682 hom. )

Consequence

SLC26A4
NM_000441.2 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:12

Conservation

PhyloP100: 2.07

Publications

3 publications found

Variant links:

Genes affected

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

SLC26A4 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 4
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
Pendred syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
athyreosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
thyroid hypoplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC26A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

For more information check the summary or visit ClinGen Evidence Repository.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2 link	c.1708-18T>A		intron_variant	Intron 15 of 20	ENST00000644269.2	NP_000432.1	O43511-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A4	ENST00000644269.2 link	c.1708-18T>A	intron_variant	Intron 15 of 20		NM_000441.2	ENSP00000494017.1	O43511-1
SLC26A4	ENST00000480841.5 link	n.557-18T>A	intron_variant	Intron 6 of 7	3
SLC26A4	ENST00000492030.2 link	n.91-744T>A	intron_variant	Intron 1 of 5	5
SLC26A4	ENST00000644846.1 link	n.418-18T>A	intron_variant	Intron 5 of 9			ENSP00000494344.1	A0A2R8Y4W7

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

3584

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00562

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0242

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00745

Gnomad FIN

AF:

0.0569

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0325

Gnomad OTH

AF:

0.0230

GnomAD2 exomes

AF:

0.0256

AC:

6412

AN:

250804

AF XY:

0.0249

show subpopulations

Gnomad AFR exome

AF:

0.00551

Gnomad AMR exome

AF:

0.0181

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0574

Gnomad NFE exome

AF:

0.0342

Gnomad OTH exome

AF:

0.0244

GnomAD4 exome

AF:

0.0295

AC:

39493

AN:

1338334

Hom.:

682

Cov.:

AF XY:

0.0287

AC XY:

19299

AN XY:

673334

show subpopulations

African (AFR)

AF:

0.00451

AC:

140

AN:

31068

American (AMR)

AF:

0.0178

AC:

791

AN:

44536

Ashkenazi Jewish (ASJ)

AF:

0.0166

AC:

422

AN:

25398

East Asian (EAS)

AF:

0.00

AC:

AN:

39134

South Asian (SAS)

AF:

0.00875

AC:

732

AN:

83684

European-Finnish (FIN)

AF:

0.0560

AC:

2982

AN:

53264

Middle Eastern (MID)

AF:

0.0203

AC:

112

AN:

5512

European-Non Finnish (NFE)

AF:

0.0329

AC:

32853

AN:

999452

Other (OTH)

AF:

0.0260

AC:

1461

AN:

56286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1811

3621

5432

7242

9053

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1168

2336

3504

4672

5840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0236

AC:

3588

AN:

152270

Hom.:

Cov.:

AF XY:

0.0236

AC XY:

1756

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00561

AC:

233

AN:

41568

American (AMR)

AF:

0.0241

AC:

369

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0182

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00787

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0569

AC:

604

AN:

10608

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0325

AC:

2210

AN:

68008

Other (OTH)

AF:

0.0232

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

176

351

527

702

878

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0260

Hom.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 14, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:5

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23280318) -

Pendred syndrome

Benign:2

Mar 18, 2020

ClinGen Hearing Loss Variant Curation Expert Panel

Significance:Benign

Review Status:reviewed by expert panel

Collection Method:curation

The filtering allele frequency (the lower threshold of the 95% CI of 1456/25104) of the c.1708-18T>A variant in the SLC26A4 gene is 5.55% for European (Finnish) chromosomes by gnomAD v2.1.1, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BA1). This silent variant in SLC26A4 is not predicted by the computational prediction analysis using MaxEntScan to impact splicing (BP7, BP4). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BA1, BP7, BP4. -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over