rs16856470

Variant names:

• chr1-205920201-C-T
• rs16856470
• NM_052934.4:c.2085G>A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_052934.4(SLC26A9):​c.2085G>A​(p.Val695Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,613,834 control chromosomes in the GnomAD database, including 4,294 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (385 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3909 hom.)
• Consequence: SLC26A9 NM_052934.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.01

Genes affected

SLC26A9 (HGNC:14469): (solute carrier family 26 member 9) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures yet have markedly different tissue expression patterns. The product of this gene is a highly selective chloride ion channel regulated by WNK kinases. Alternative splicing results in multiple transcript variants encoding differing isoforms.[provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 1-205920201-C-T is Benign according to our data. Variant chr1-205920201-C-T is described in ClinVar as [Benign]. Clinvar id is 403453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.01 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.2085G>A	p.Val695Val	synonymous_variant	Exon 18 of 21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3	c.2085G>A	p.Val695Val	synonymous_variant	Exon 18 of 22		NP_599152.2
SLC26A9	XM_011509121.3	c.1818G>A	p.Val606Val	synonymous_variant	Exon 17 of 20		XP_011507423.1
SLC26A9	XM_011509122.3	c.1593G>A	p.Val531Val	synonymous_variant	Exon 15 of 18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8	c.2085G>A	p.Val695Val	synonymous_variant	Exon 18 of 21	1	NM_052934.4	ENSP00000356103.3
SLC26A9	ENST00000340781.8	c.2085G>A	p.Val695Val	synonymous_variant	Exon 17 of 21	1		ENSP00000341682.4
SLC26A9	ENST00000367134.2	c.2085G>A	p.Val695Val	synonymous_variant	Exon 18 of 22	5		ENSP00000356102.2
SLC26A9	ENST00000491127.5	n.1469G>A		non_coding_transcript_exon_variant	Exon 10 of 13	2

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10653 AN: 152126 Hom.: 384 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0936

GnomAD3 exomes AF: 0.0626 AC: 15744 AN: 251478 Hom.: 621 AF XY: 0.0627 AC XY: 8527 AN XY: 135910

Gnomad AFR exome AF: 0.0773

Gnomad AMR exome AF: 0.0446

Gnomad ASJ exome AF: 0.130

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0323

Gnomad FIN exome AF: 0.0462

Gnomad NFE exome AF: 0.0803

Gnomad OTH exome AF: 0.0813

GnomAD4 exome AF: 0.0703 AC: 102798 AN: 1461590 Hom.: 3909 Cov.: 31 AF XY: 0.0700 AC XY: 50889 AN XY: 727120

Gnomad4 AFR exome AF: 0.0713

Gnomad4 AMR exome AF: 0.0465

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0322

Gnomad4 FIN exome AF: 0.0473

Gnomad4 NFE exome AF: 0.0759

Gnomad4 OTH exome AF: 0.0742

GnomAD4 genome AF: 0.0700 AC: 10655 AN: 152244 Hom.: 385 Cov.: 32 AF XY: 0.0670 AC XY: 4987 AN XY: 74442

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0317

Gnomad4 FIN AF: 0.0425

Gnomad4 NFE AF: 0.0773

Gnomad4 OTH AF: 0.0931

Alfa AF: 0.0805 Hom.: 873

Bravo AF: 0.0733

Asia WGS AF: 0.0160 AC: 54 AN: 3478

EpiCase AF: 0.0881

EpiControl AF: 0.0901

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	11
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs16856470; hg19: chr1-205889329; COSMIC: COSV61605873; COSMIC: COSV61605873;