Variant 7-103411334-G-A 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.570+86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 1,522,520 control chromosomes in the GnomAD database, including 5,660 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 452 hom., cov: 32)

Exomes 𝑓: 0.084 ( 5208 hom. )

Consequence

SLC26A5
NM_198999.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.55

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=-0.92).

BP6

Variant 7-103411334-G-A is Benign according to our data. Variant chr7-103411334-G-A is described in ClinVar as [Benign]. Clinvar id is 1293716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.123 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.570+86C>T		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.570+86C>T		intron_variant		1	NM_198999.3	ENSP00000304783	P4	P58743-1

Frequencies

GnomAD3 genomes

AF:

0.0699

AC:

10624

AN:

152018

Hom.:

454

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0230

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.0488

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0944

Gnomad FIN

AF:

0.0737

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0803

Gnomad OTH

AF:

0.0560

GnomAD4 exome

AF:

0.0837

AC:

114762

AN:

1370382

Hom.:

5208

AF XY:

0.0835

AC XY:

56763

AN XY:

680014

show subpopulations

Gnomad4 AFR exome

AF:

0.0199

Gnomad4 AMR exome

AF:

0.173

Gnomad4 ASJ exome

AF:

0.0476

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.0985

Gnomad4 FIN exome

AF:

0.0753

Gnomad4 NFE exome

AF:

0.0816

Gnomad4 OTH exome

AF:

0.0808

GnomAD4 genome

AF:

0.0699

AC:

10632

AN:

152138

Hom.:

452

Cov.:

AF XY:

0.0719

AC XY:

5347

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0231

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.0488

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.0936

Gnomad4 FIN

AF:

0.0737

Gnomad4 NFE

AF:

0.0803

Gnomad4 OTH

AF:

0.0616

Alfa

AF:

0.0328

Hom.:

Bravo

AF:

0.0720

Asia WGS

AF:

0.142

AC:

492

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0030

DANN

Benign

0.50

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

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