rs9438438

chr1-205914934-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The ENST00000340781.8(SLC26A9):c.2622A>G(p.Pro874=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,614,076 control chromosomes in the GnomAD database, including 6,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (894 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5370 hom.)
• Consequence: SLC26A9 ENST00000340781.8 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0320

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-205914934-T-C is Benign according to our data. Variant chr1-205914934-T-C is described in ClinVar as [Benign]. Clinvar id is 403450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.032 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A9	NM_052934.4	c.*423A>G		3_prime_UTR_variant	21/21	ENST00000367135.8
SLC26A9	NM_134325.3	c.2622A>G	p.Pro874=	synonymous_variant	22/22
SLC26A9	XM_011509121.3	c.*423A>G		3_prime_UTR_variant	20/20
SLC26A9	XM_011509122.3	c.*423A>G		3_prime_UTR_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A9	ENST00000340781.8	c.2622A>G	p.Pro874=	synonymous_variant	21/21	1
SLC26A9	ENST00000367135.8	c.*423A>G		3_prime_UTR_variant	21/21	1	NM_052934.4	P1
SLC26A9	ENST00000367134.2	c.2622A>G	p.Pro874=	synonymous_variant	22/22	5
SLC26A9	ENST00000491127.5	n.2183A>G		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15336 AN: 152138 Hom.: 890 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.0742 AC: 18631 AN: 251188 Hom.: 884 AF XY: 0.0724 AC XY: 9832 AN XY: 135718

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.0523

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0315

Gnomad FIN exome AF: 0.0623

Gnomad NFE exome AF: 0.0902

Gnomad OTH exome AF: 0.0860

GnomAD4 exome AF: 0.0824 AC: 120443 AN: 1461820 Hom.: 5370 Cov.: 32 AF XY: 0.0811 AC XY: 58985 AN XY: 727220

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0543

Gnomad4 ASJ exome AF: 0.108

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0307

Gnomad4 FIN exome AF: 0.0640

Gnomad4 NFE exome AF: 0.0882

Gnomad4 OTH exome AF: 0.0789

GnomAD4 genome AF: 0.101 AC: 15353 AN: 152256 Hom.: 894 Cov.: 32 AF XY: 0.0965 AC XY: 7182 AN XY: 74438

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0752

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0259

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.0886

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0927 Hom.: 686

Bravo AF: 0.106

EpiCase AF: 0.0965

EpiControl AF: 0.0978

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.8
Dann	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs9438438; hg19: chr1-205884062;