rs62482415

chr7-103389468-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.975

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 -14 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_single_submitter, 1 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	UniProt
SLC26A5	NM_198999.3	c.1312-44T>C		intron_variant		ENST00000306312.8

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20838 AN: 151850 Hom.: 1565 Cov.: 32

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

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.: 18 AF XY: 0.146 AC XY: 94505 AN XY: 649486

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.: 32 AF XY: 0.142 AC XY: 10514 AN XY: 74256

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs62482415; hg19: chr7-103029915; COSMIC: COSV59707468;