rs72655395

Positions:

• chr7-103380593-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.1515-44C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,551,366 control chromosomes in the GnomAD database, including 248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (128 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (120 hom.)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.143

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=-0.93).
• BP6: Variant 7-103380593-G-A is Benign according to our data. Variant chr7-103380593-G-A is described in ClinVar as [Benign]. Clinvar id is 676192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.079 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.1515-44C>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.1515-44C>T		intron_variant		1	NM_198999.3	ENSP00000304783	P4

Frequencies

GnomAD3 genomes AF: 0.0231 AC: 3506 AN: 151996 Hom.: 129 Cov.: 32

Gnomad AFR AF: 0.0811

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0134

GnomAD3 exomes AF: 0.00619 AC: 1551 AN: 250544 Hom.: 50 AF XY: 0.00461 AC XY: 624 AN XY: 135370

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.00383

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000655

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000194

Gnomad OTH exome AF: 0.00213

GnomAD4 exome AF: 0.00240 AC: 3357 AN: 1399252 Hom.: 120 Cov.: 23 AF XY: 0.00207 AC XY: 1447 AN XY: 699680

Gnomad4 AFR exome AF: 0.0850

Gnomad4 AMR exome AF: 0.00417

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000102

Gnomad4 SAS exome AF: 0.000141

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000967

Gnomad4 OTH exome AF: 0.00522

GnomAD4 genome AF: 0.0231 AC: 3521 AN: 152114 Hom.: 128 Cov.: 32 AF XY: 0.0225 AC XY: 1675 AN XY: 74376

Gnomad4 AFR AF: 0.0813

Gnomad4 AMR AF: 0.00693

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0139 Hom.: 25

Bravo AF: 0.0257

Asia WGS AF: 0.00491 AC: 17 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 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.7
DANN	Benign	0.56

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: rs72655395; hg19: chr7-103021040;