7-107710094-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000441.2(SLC26A4):​c.2130C>T​(p.Asp710Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,611,564 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 78 hom., cov: 32)
Exomes 𝑓: 0.0021 ( 97 hom. )

Consequence

SLC26A4
NM_000441.2 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.234
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 7-107710094-C-T is Benign according to our data. Variant chr7-107710094-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 43538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107710094-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.234 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0636 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC26A4NM_000441.2 linkc.2130C>T p.Asp710Asp synonymous_variant Exon 19 of 21 ENST00000644269.2 NP_000432.1 O43511-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC26A4ENST00000644269.2 linkc.2130C>T p.Asp710Asp synonymous_variant Exon 19 of 21 NM_000441.2 ENSP00000494017.1 O43511-1
SLC26A4ENST00000644846.1 linkn.*32C>T non_coding_transcript_exon_variant Exon 8 of 10 ENSP00000494344.1 A0A2R8Y4W7
SLC26A4ENST00000644846.1 linkn.*32C>T 3_prime_UTR_variant Exon 8 of 10 ENSP00000494344.1 A0A2R8Y4W7
SLC26A4ENST00000492030.2 linkn.377-61C>T intron_variant Intron 3 of 5 5

Frequencies

GnomAD3 genomes
AF:
0.0189
AC:
2877
AN:
152152
Hom.:
78
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0656
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00700
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000620
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000309
Gnomad OTH
AF:
0.0134
GnomAD3 exomes
AF:
0.00492
AC:
1237
AN:
251266
Hom.:
39
AF XY:
0.00362
AC XY:
492
AN XY:
135784
show subpopulations
Gnomad AFR exome
AF:
0.0663
Gnomad AMR exome
AF:
0.00278
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000196
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000317
Gnomad OTH exome
AF:
0.00343
GnomAD4 exome
AF:
0.00210
AC:
3062
AN:
1459294
Hom.:
97
Cov.:
29
AF XY:
0.00179
AC XY:
1302
AN XY:
726174
show subpopulations
Gnomad4 AFR exome
AF:
0.0706
Gnomad4 AMR exome
AF:
0.00324
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000267
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000189
Gnomad4 OTH exome
AF:
0.00494
GnomAD4 genome
AF:
0.0190
AC:
2887
AN:
152270
Hom.:
78
Cov.:
32
AF XY:
0.0180
AC XY:
1341
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0657
Gnomad4 AMR
AF:
0.00699
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000309
Gnomad4 OTH
AF:
0.0133
Alfa
AF:
0.00571
Hom.:
17
Bravo
AF:
0.0220
Asia WGS
AF:
0.00404
AC:
14
AN:
3478
EpiCase
AF:
0.000545
EpiControl
AF:
0.000296

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Sep 16, 2010
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is classified as benign due to a common occurrence in control poula tions (dbSNP - rs17154347). -

Jan 17, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:4
Jan 20, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Dec 17, 2020
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

May 23, 2018
Athena Diagnostics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Pendred syndrome Benign:2
Sep 16, 2020
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Autosomal recessive nonsyndromic hearing loss 4 Benign:1
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.30
CADD
Benign
8.5
DANN
Benign
0.58

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17154347; hg19: chr7-107350539; API