Genetic Variant SLC26A4:c.-4+90T>G (chr7-107660945-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000441.2(SLC26A4):c.-4+90T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,242 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 Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 175 hom., cov: 32)

Exomes 𝑓: 0.048 ( 0 hom. )

Consequence

SLC26A4
NM_000441.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.35

Publications

0 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 links:

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

SLC26A4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-107660945-T-G is Benign according to our data. Variant chr7-107660945-T-G is described in ClinVar as [Benign]. Clinvar id is 1267269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2 link	c.-4+90T>G		intron_variant	Intron 1 of 20	ENST00000644269.2	NP_000432.1	O43511-1
SLC26A4-AS1	NR_028137.1 link	n.197+657A>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2 link	c.-4+90T>G		intron_variant	Intron 1 of 20		NM_000441.2	ENSP00000494017.1		O43511-1

Frequencies

GnomAD3 genomes

AF:

0.0447

AC:

6795

AN:

151958

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0498

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.0241

Gnomad FIN

AF:

0.0328

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0520

Gnomad OTH

AF:

0.0417

GnomAD4 exome

AF:

0.0476

AC:

AN:

168

Hom.:

Cov.:

AF XY:

0.0614

AC XY:

AN XY:

114

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0352

AC:

AN:

142

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0447

AC:

6802

AN:

152074

Hom.:

175

Cov.:

AF XY:

0.0430

AC XY:

3194

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0500

AC:

2073

AN:

41490

American (AMR)

AF:

0.0293

AC:

448

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

112

AN:

3468

East Asian (EAS)

AF:

0.00136

AC:

AN:

5154

South Asian (SAS)

AF:

0.0242

AC:

116

AN:

4800

European-Finnish (FIN)

AF:

0.0328

AC:

348

AN:

10614

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0520

AC:

3535

AN:

67950

Other (OTH)

AF:

0.0413

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

338

676

1013

1351

1689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0494

Hom.:

Bravo

AF:

0.0440

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.76

(source)

DANN

Benign

0.43

PhyloP100

-1.4

PromoterAI

0.017

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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chr7-107660945-T-G

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