chr7-103374133-A-G

Position:

• chr7-103374133-A-G

Variant summary

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

The ENST00000339444.10(SLC26A5):​c.2041+2675T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0608 in 1,183,334 control chromosomes in the GnomAD database, including 3,973 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1718 hom., cov: 32)
  • Exomes 𝑓: 0.053 (2255 hom.)
• Consequence: SLC26A5 ENST00000339444.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500

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=-0.91).
• BP6: Variant 7-103374133-A-G is Benign according to our data. Variant chr7-103374133-A-G is described in ClinVar as [Benign]. Clinvar id is 1290192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A5	NM_001321787.2	c.1945+2675T>C		intron_variant			NP_001308716.1
SLC26A5	NM_206883.3	c.2041+2675T>C		intron_variant			NP_996766.1
SLC26A5	NM_206884.3	c.1514+14875T>C		intron_variant			NP_996767.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000339444.10	c.2041+2675T>C		intron_variant		1		ENSP00000342396
SLC26A5	ENST00000356767.8	c.972-21207T>C		intron_variant		1		ENSP00000349210
SLC26A5	ENST00000393735.6	c.1514+14875T>C		intron_variant		1		ENSP00000377336

Frequencies

GnomAD3 genomes AF: 0.112 AC: 16959 AN: 152050 Hom.: 1719 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00682

Gnomad FIN AF: 0.0943

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0875

GnomAD4 exome AF: 0.0533 AC: 54998 AN: 1031166 Hom.: 2255 AF XY: 0.0525 AC XY: 25716 AN XY: 490112

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.0371

Gnomad4 ASJ exome AF: 0.0195

Gnomad4 EAS exome AF: 0.000165

Gnomad4 SAS exome AF: 0.0102

Gnomad4 FIN exome AF: 0.0877

Gnomad4 NFE exome AF: 0.0504

Gnomad4 OTH exome AF: 0.0547

GnomAD4 genome AF: 0.112 AC: 16980 AN: 152168 Hom.: 1718 Cov.: 32 AF XY: 0.109 AC XY: 8131 AN XY: 74390

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00683

Gnomad4 FIN AF: 0.0943

Gnomad4 NFE AF: 0.0499

Gnomad4 OTH AF: 0.0866

Alfa AF: 0.0896 Hom.: 307

Bravo AF: 0.116

Asia WGS AF: 0.0190 AC: 65 AN: 3476

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	Mar 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.42

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28375913; hg19: chr7-103014580;