rs56373660

Positions:

• chr7-103389473-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198999.3(SLC26A5):​c.1312-49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 1,361,026 control chromosomes in the GnomAD database, including 5,155 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (457 hom., cov: 32)
  • Exomes 𝑓: 0.084 (4698 hom.)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.110

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 7-103389473-G-A is Benign according to our data. Variant chr7-103389473-G-A is described in ClinVar as [Benign]. Clinvar id is 1239804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.1312-49C>T		intron_variant		ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8	c.1312-49C>T		intron_variant		1	NM_198999.3	ENSP00000304783	P4

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10563 AN: 151948 Hom.: 459 Cov.: 32

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0456

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0943

Gnomad FIN AF: 0.0736

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0804

Gnomad OTH AF: 0.0555

GnomAD3 exomes AF: 0.0913 AC: 22705 AN: 248672 Hom.: 1240 AF XY: 0.0885 AC XY: 11891 AN XY: 134428

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.0461

Gnomad EAS exome AF: 0.115

Gnomad SAS exome AF: 0.100

Gnomad FIN exome AF: 0.0751

Gnomad NFE exome AF: 0.0768

Gnomad OTH exome AF: 0.0815

GnomAD4 exome AF: 0.0843 AC: 101944 AN: 1208958 Hom.: 4698 Cov.: 17 AF XY: 0.0840 AC XY: 51564 AN XY: 613998

Gnomad4 AFR exome AF: 0.0201

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.0445

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.0982

Gnomad4 FIN exome AF: 0.0745

Gnomad4 NFE exome AF: 0.0815

Gnomad4 OTH exome AF: 0.0795

GnomAD4 genome AF: 0.0695 AC: 10571 AN: 152068 Hom.: 457 Cov.: 32 AF XY: 0.0715 AC XY: 5311 AN XY: 74306

Gnomad4 AFR AF: 0.0226

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0456

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.0936

Gnomad4 FIN AF: 0.0736

Gnomad4 NFE AF: 0.0804

Gnomad4 OTH AF: 0.0611

Alfa AF: 0.0697 Hom.: 71

Bravo AF: 0.0714

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.78
CADD	Benign	1.5
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs56373660; hg19: chr7-103029920;