Variant rs62482415 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198999.3(SLC26A5):c.1312-44T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,439,138 control chromosomes in the GnomAD database, including 15,869 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1569 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14300 hom. )

Consequence

SLC26A5
NM_198999.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.975

Variant links:

Genes affected

SLC26A5 (HGNC:9359): (solute carrier family 26 member 5) This gene encodes a member of the SLC26A/SulP transporter family. The protein functions as a molecular motor in motile outer hair cells (OHCs) of the cochlea, inducing changes in cell length that act to amplify sound levels. The transmembrane protein is an incomplete anion transporter, and does not allow anions to cross the cell membrane but instead undergoes a conformational change in response to changes in intracellular Cl- levels that results in a change in cell length. The protein functions at microsecond rates, which is several orders of magnitude faster than conventional molecular motor proteins. Mutations in this gene are potential candidates for causing neurosensory deafness. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2009]

SLC26A5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 7-103389468-A-G is Benign according to our data. Variant chr7-103389468-A-G is described in ClinVar as [Benign]. Clinvar id is 1237911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A5	NM_198999.3 linkuse as main transcript	c.1312-44T>C		intron_variant		ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8 linkuse as main transcript	c.1312-44T>C		intron_variant		1	NM_198999.3	ENSP00000304783	P4	P58743-1

Frequencies

GnomAD3 genomes

AF:

0.137

AC:

20838

AN:

151850

Hom.:

1565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.0943

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.0906

Gnomad EAS

AF:

0.0677

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.151

AC:

37594

AN:

249428

Hom.:

3152

AF XY:

0.152

AC XY:

20430

AN XY:

134810

show subpopulations

Gnomad AFR exome

AF:

0.117

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.0849

Gnomad EAS exome

AF:

0.0629

Gnomad SAS exome

AF:

0.183

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.136

GnomAD4 exome

AF:

0.145

AC:

186336

AN:

1287170

Hom.:

14300

Cov.:

AF XY:

0.146

AC XY:

94505

AN XY:

649486

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.187

Gnomad4 ASJ exome

AF:

0.0855

Gnomad4 EAS exome

AF:

0.0754

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.141

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.137

AC:

20854

AN:

151968

Hom.:

1569

Cov.:

AF XY:

0.142

AC XY:

10514

AN XY:

74256

show subpopulations

Gnomad4 AFR

AF:

0.115

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.0906

Gnomad4 EAS

AF:

0.0679

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.130

Hom.:

399

Bravo

AF:

0.129

Asia WGS

AF:

0.112

AC:

389

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over