rs56305143

Variant names:

• chr7-103411334-G-A
• rs56305143
• NM_198999.3:c.570+86C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 VariationId 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 rank	MANE	Protein	UniProt
SLC26A5	NM_198999.3	c.570+86C>T		intron_variant	Intron 6 of 19	ENST00000306312.8	NP_945350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A5	ENST00000306312.8	c.570+86C>T		intron_variant	Intron 6 of 19	1	NM_198999.3	ENSP00000304783.3
SLC26A5	ENST00000393727.5	c.570+86C>T		intron_variant	Intron 4 of 17	1		ENSP00000377328.1
SLC26A5	ENST00000393723.2	c.570+86C>T		intron_variant	Intron 4 of 16	1		ENSP00000377324.1

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

African (AFR) AF: 0.0199 AC: 631 AN: 31658

American (AMR) AF: 0.173 AC: 7235 AN: 41884

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 1102 AN: 23158

East Asian (EAS) AF: 0.110 AC: 4282 AN: 39014

South Asian (SAS) AF: 0.0985 AC: 7598 AN: 77122

European-Finnish (FIN) AF: 0.0753 AC: 3868 AN: 51384

Middle Eastern (MID) AF: 0.0522 AC: 286 AN: 5474

European-Non Finnish (NFE) AF: 0.0816 AC: 85155 AN: 1043680

Other (OTH) AF: 0.0808 AC: 4605 AN: 57008

GnomAD4 genome AF: 0.0699 AC: 10632 AN: 152138 Hom.: 452 Cov.: 32 AF XY: 0.0719 AC XY: 5347 AN XY: 74368

African (AFR) AF: 0.0231 AC: 957 AN: 41514

American (AMR) AF: 0.128 AC: 1960 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0488 AC: 169 AN: 3466

East Asian (EAS) AF: 0.113 AC: 581 AN: 5162

South Asian (SAS) AF: 0.0936 AC: 450 AN: 4806

European-Finnish (FIN) AF: 0.0737 AC: 780 AN: 10588

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0803 AC: 5459 AN: 67992

Other (OTH) AF: 0.0616 AC: 130 AN: 2112

Alfa AF: 0.0324 Hom.: 18

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 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	-0.92
CADD	Benign	0.0030
DANN	Benign	0.50
PhyloP100		-1.6
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: rs56305143; hg19: chr7-103051781; COSMIC: COSV59697863;