rs28375913

Variant names:

• chr7-103374133-A-G
• rs28375913
• ENST00000339444.10:c.2041+2675T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_206883.3(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 NM_206883.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia
• 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206883.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A5	NM_206883.3		c.2041+2675T>C		intron	N/A	NP_996766.1	P58743-2
	SLC26A5	NM_001321787.2		c.1945+2675T>C		intron	N/A	NP_001308716.1
	SLC26A5	NM_206884.3		c.1514+14875T>C		intron	N/A	NP_996767.1	P58743-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A5	ENST00000339444.10	TSL:1	c.2041+2675T>C		intron	N/A	ENSP00000342396.6	P58743-2
	SLC26A5	ENST00000393735.6	TSL:1	c.1514+14875T>C		intron	N/A	ENSP00000377336.2	P58743-3
	SLC26A5	ENST00000356767.8	TSL:1	c.972-21207T>C		intron	N/A	ENSP00000349210.4	P58743-4

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

African (AFR) AF: 0.297 AC: 6489 AN: 21878

American (AMR) AF: 0.0371 AC: 336 AN: 9054

Ashkenazi Jewish (ASJ) AF: 0.0195 AC: 243 AN: 12488

East Asian (EAS) AF: 0.000165 AC: 3 AN: 18230

South Asian (SAS) AF: 0.0102 AC: 387 AN: 37790

European-Finnish (FIN) AF: 0.0877 AC: 1082 AN: 12334

Middle Eastern (MID) AF: 0.0241 AC: 62 AN: 2574

European-Non Finnish (NFE) AF: 0.0504 AC: 44202 AN: 876672

Other (OTH) AF: 0.0547 AC: 2194 AN: 40146

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

African (AFR) AF: 0.278 AC: 11520 AN: 41448

American (AMR) AF: 0.0512 AC: 784 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0179 AC: 62 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00683 AC: 33 AN: 4832

European-Finnish (FIN) AF: 0.0943 AC: 999 AN: 10594

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0499 AC: 3394 AN: 68012

Other (OTH) AF: 0.0866 AC: 183 AN: 2114

Alfa AF: 0.0847 Hom.: 430

Bravo AF: 0.116

Asia WGS AF: 0.0190 AC: 65 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.42
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs28375913; hg19: chr7-103014580;