rs7811324

Variant names:

• chr7-107661656-C-A
• rs7811324
• NM_000441.2:c.15C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-107661656-C-A
• chr7-107661656-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_000441.2(SLC26A4):​c.15C>A​(p.Gly5Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,567,138 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G5G) has been classified as Likely benign. The gene SLC26A4 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.0062 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00069 (7 hom.)
• Consequence: SLC26A4 NM_000441.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:10
• Conservation: PhyloP100: 0.365
• Publications: 3 publications found

Genes affected

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]

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

ACMG classification

Specifications for SLC26A4 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 7-107661656-C-A is Benign according to our data. Variant chr7-107661656-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 43515.
• BP7: Synonymous conserved (PhyloP=0.365 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00617 (940/152384) while in subpopulation AFR AF = 0.0213 (886/41596). AF 95% confidence interval is 0.0201. There are 8 homozygotes in GnomAd4. There are 467 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 8 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000441.2. 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
	SLC26A4	NM_000441.2	MANE Select	c.15C>A	p.Gly5Gly	synonymous	Exon 2 of 21	NP_000432.1	O43511-1
	SLC26A4-AS1	NR_028137.1		n.143G>T		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.15C>A	p.Gly5Gly	synonymous	Exon 2 of 21	ENSP00000494017.1	O43511-1
	SLC26A4	ENST00000888701.1		c.15C>A	p.Gly5Gly	synonymous	Exon 1 of 20	ENSP00000558760.1
	SLC26A4	ENST00000888700.1		c.15C>A	p.Gly5Gly	synonymous	Exon 2 of 20	ENSP00000558759.1

Frequencies

GnomAD3 genomes AF: 0.00617 AC: 939 AN: 152266 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00145 AC: 256 AN: 176868 AF XY: 0.00108

Gnomad AFR exome AF: 0.0229

Gnomad AMR exome AF: 0.000968

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000900

Gnomad OTH exome AF: 0.000833

GnomAD4 exome AF: 0.000688 AC: 973 AN: 1414754 Hom.: 7 Cov.: 30 AF XY: 0.000619 AC XY: 434 AN XY: 700636

African (AFR) AF: 0.0239 AC: 782 AN: 32728

American (AMR) AF: 0.00113 AC: 44 AN: 38924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25476

East Asian (EAS) AF: 0.00 AC: 0 AN: 37794

South Asian (SAS) AF: 0.0000246 AC: 2 AN: 81282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40026

Middle Eastern (MID) AF: 0.00215 AC: 12 AN: 5578

European-Non Finnish (NFE) AF: 0.0000494 AC: 54 AN: 1093998

Other (OTH) AF: 0.00134 AC: 79 AN: 58948

GnomAD4 genome AF: 0.00617 AC: 940 AN: 152384 Hom.: 8 Cov.: 32 AF XY: 0.00627 AC XY: 467 AN XY: 74532

African (AFR) AF: 0.0213 AC: 886 AN: 41596

American (AMR) AF: 0.00202 AC: 31 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68034

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.000475 Hom.: 0

Bravo AF: 0.00676

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	1	3	Pendred syndrome (4)
-	1	1	Autosomal recessive nonsyndromic hearing loss 4 (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism

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: rs7811324; hg19: chr7-107302101;