rs568363861

Variant names:

• chr7-107660702-G-A
• rs568363861
• ENST00000658036.1:n.1195C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-107660702-G-A
• chr7-107660702-G-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000658036.1(SLC26A4-AS1):​n.1195C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 152,336 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.00016 (0 hom., cov: 32)
• Consequence: SLC26A4-AS1 ENST00000658036.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.478

Genes affected

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4-AS1	NR_028137.1	n.198-496C>T		intron_variant	Intron 1 of 1
SLC26A4	NM_000441.2	c.-157G>A		upstream_gene_variant		ENST00000644269.2	NP_000432.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2	c.-157G>A		upstream_gene_variant			NM_000441.2	ENSP00000494017.1

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152218 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152336 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74496

African (AFR) AF: 0.00 AC: 0 AN: 41584

American (AMR) AF: 0.00118 AC: 18 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68016

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000204

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.-157G>A variant in SLC26A4 has not been previously reported in individuals with hearing loss, but has been identified in 0.1% (1/838) of Latino chromosome s by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs568363861). Although this variant has been seen in the general populatio n, its frequency is not high enough to rule out a pathogenic role. This variant is in the 5' untranslated region (UTR) of the SLC26A4 gene. It is unknown and c annot be predicted whether or not this variant impacts the protein. In summary, the clinical significance of this variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.89
PhyloP100		-0.48
PromoterAI		-0.053	Neutral

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

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Other links and lift over

dbSNP: rs568363861; hg19: chr7-107301147;