rs56305143

Positions:

• chr7-103411334-G-A
• chr7-103411334-G-C

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.55

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=-0.92).
• 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	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	c.570+86C>T		intron_variant		1	NM_198999.3	ENSP00000304783	P4

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10624 AN: 152018 Hom.: 454 Cov.: 32

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

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.: 32 AF XY: 0.0719 AC XY: 5347 AN XY: 74368

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.: 17

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

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

Other links and lift over

dbSNP: rs56305143; hg19: chr7-103051781; COSMIC: COSV59697863;