ENST00000340781.8:c.2410A>G

Variant names:

• chr1-205915146-T-C
• rs6669481
• ENST00000340781.8:c.2410A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000340781.8(SLC26A9):​c.2410A>G​(p.Arg804Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,613,058 control chromosomes in the GnomAD database, including 13,016 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (4034 hom., cov: 32)
  • Exomes 𝑓: 0.095 (8982 hom.)
• Consequence: SLC26A9 ENST00000340781.8 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.509
• Publications: 18 publications found

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]

SLC26A9 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.041791E-4).
• BP6: Variant 1-205915146-T-C is Benign according to our data. Variant chr1-205915146-T-C is described in ClinVar as [Benign]. Clinvar id is 403451.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.*211A>G		3_prime_UTR_variant	Exon 21 of 21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3	c.2410A>G	p.Arg804Gly	missense_variant	Exon 22 of 22		NP_599152.2
SLC26A9	XM_011509121.3	c.*211A>G		3_prime_UTR_variant	Exon 20 of 20		XP_011507423.1
SLC26A9	XM_011509122.3	c.*211A>G		3_prime_UTR_variant	Exon 18 of 18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000340781.8	c.2410A>G	p.Arg804Gly	missense_variant	Exon 21 of 21	1		ENSP00000341682.4
SLC26A9	ENST00000367135.8	c.*211A>G		3_prime_UTR_variant	Exon 21 of 21	1	NM_052934.4	ENSP00000356103.3
SLC26A9	ENST00000367134.2	c.2410A>G	p.Arg804Gly	missense_variant	Exon 22 of 22	5		ENSP00000356102.2
SLC26A9	ENST00000491127.5	n.1971A>G		non_coding_transcript_exon_variant	Exon 13 of 13	2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27221 AN: 151786 Hom.: 4023 Cov.: 32

Gnomad AFR AF: 0.408

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0942

Gnomad OTH AF: 0.173

GnomAD2 exomes AF: 0.0995 AC: 24903 AN: 250402 AF XY: 0.0917

Gnomad AFR exome AF: 0.417

Gnomad AMR exome AF: 0.0709

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0983

Gnomad OTH exome AF: 0.0981

GnomAD4 exome AF: 0.0948 AC: 138455 AN: 1461154 Hom.: 8982 Cov.: 32 AF XY: 0.0919 AC XY: 66778 AN XY: 726772

African (AFR) AF: 0.427 AC: 14300 AN: 33470

American (AMR) AF: 0.0751 AC: 3355 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2900 AN: 26088

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39684

South Asian (SAS) AF: 0.0209 AC: 1797 AN: 86186

European-Finnish (FIN) AF: 0.101 AC: 5402 AN: 53402

Middle Eastern (MID) AF: 0.136 AC: 785 AN: 5762

European-Non Finnish (NFE) AF: 0.0934 AC: 103787 AN: 1111514

Other (OTH) AF: 0.101 AC: 6126 AN: 60362

GnomAD4 genome AF: 0.180 AC: 27272 AN: 151904 Hom.: 4034 Cov.: 32 AF XY: 0.173 AC XY: 12881 AN XY: 74242

African (AFR) AF: 0.408 AC: 16860 AN: 41354

American (AMR) AF: 0.121 AC: 1852 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.113 AC: 391 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4816

European-Finnish (FIN) AF: 0.103 AC: 1093 AN: 10580

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0942 AC: 6402 AN: 67946

Other (OTH) AF: 0.172 AC: 363 AN: 2110

Alfa AF: 0.119 Hom.: 6162

Bravo AF: 0.193

TwinsUK AF: 0.0903 AC: 335

ALSPAC AF: 0.0856 AC: 330

ESP6500AA AF: 0.400 AC: 1764

ESP6500EA AF: 0.0964 AC: 829

ExAC AF: 0.105 AC: 12713

Asia WGS AF: 0.0400 AC: 137 AN: 3478

EpiCase AF: 0.104

EpiControl AF: 0.106

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_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.9
DANN	Benign	0.90
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.43	.;T
MetaRNN	Benign	0.00040	T;T
MetaSVM	Benign	-0.98	T
PhyloP100		0.51
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.055	T;T
Vest4		0.049
MPC		0.18
ClinPred		0.015	T
GERP RS		0.71
gMVP		0.23
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs6669481; hg19: chr1-205884274; COSMIC: COSV61604404;