rs62482412

Variant names:

• chr7-103376576-C-T
• rs62482412
• NM_198999.3:c.2041+232G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198999.3(SLC26A5):​c.2041+232G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 152,120 control chromosomes in the GnomAD database, including 693 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.081 (693 hom., cov: 32)
• Consequence: SLC26A5 NM_198999.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 61

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-103376576-C-T is Benign according to our data. Variant chr7-103376576-C-T is described in ClinVar as Benign. ClinVar VariationId is 1232174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.2041+232G>A		intron_variant	Intron 19 of 19	ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8	c.2041+232G>A		intron_variant	Intron 19 of 19	1	NM_198999.3	ENSP00000304783.3
SLC26A5	ENST00000393727.5	c.2047+232G>A		intron_variant	Intron 17 of 17	1		ENSP00000377328.1
SLC26A5	ENST00000393723.2	c.1951+232G>A		intron_variant	Intron 16 of 16	1		ENSP00000377324.1

Frequencies

GnomAD3 genomes AF: 0.0807 AC: 12271 AN: 152004 Hom.: 692 Cov.: 32

Gnomad AFR AF: 0.0214

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0755

Gnomad EAS AF: 0.0731

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0908

Gnomad OTH AF: 0.0732

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0807 AC: 12274 AN: 152120 Hom.: 693 Cov.: 32 AF XY: 0.0859 AC XY: 6387 AN XY: 74380

African (AFR) AF: 0.0213 AC: 885 AN: 41496

American (AMR) AF: 0.137 AC: 2090 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0755 AC: 262 AN: 3472

East Asian (EAS) AF: 0.0731 AC: 379 AN: 5184

South Asian (SAS) AF: 0.187 AC: 902 AN: 4826

European-Finnish (FIN) AF: 0.125 AC: 1317 AN: 10560

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0908 AC: 6175 AN: 67990

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0874 Hom.: 383

Bravo AF: 0.0772

Asia WGS AF: 0.124 AC: 429 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.14
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62482412; hg19: chr7-103017023;