rs2295852

Positions:

• chr6-35955469-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052961.4(SLC26A8):​c.1915A>G​(p.Ile639Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 1,613,794 control chromosomes in the GnomAD database, including 107,216 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.42 (15087 hom., cov: 31)
  • Exomes 𝑓: 0.35 (92129 hom.)
• Consequence: SLC26A8 NM_052961.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.34

Genes affected

SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.815994E-6).
• BP6: Variant 6-35955469-T-C is Benign according to our data. Variant chr6-35955469-T-C is described in ClinVar as [Benign]. Clinvar id is 1234924.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC26A8	NM_052961.4	c.1915A>G	p.Ile639Val	missense_variant	17/20	ENST00000490799.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A8	ENST00000490799.6	c.1915A>G	p.Ile639Val	missense_variant	17/20	1	NM_052961.4	P1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63777 AN: 151864 Hom.: 15044 Cov.: 31

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.428

GnomAD3 exomes AF: 0.335 AC: 84110 AN: 251336 Hom.: 15475 AF XY: 0.333 AC XY: 45172 AN XY: 135832

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.296

Gnomad SAS exome AF: 0.285

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.350

Gnomad OTH exome AF: 0.345

GnomAD4 exome AF: 0.349 AC: 510559 AN: 1461812 Hom.: 92129 Cov.: 43 AF XY: 0.346 AC XY: 251855 AN XY: 727204

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.230

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.283

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.420 AC: 63863 AN: 151982 Hom.: 15087 Cov.: 31 AF XY: 0.414 AC XY: 30730 AN XY: 74266

Gnomad4 AFR AF: 0.647

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.429

Alfa AF: 0.360 Hom.: 26053

Bravo AF: 0.435

TwinsUK AF: 0.357 AC: 1324

ALSPAC AF: 0.361 AC: 1390

ESP6500AA AF: 0.637 AC: 2807

ESP6500EA AF: 0.349 AC: 3003

ExAC AF: 0.346 AC: 41971

Asia WGS AF: 0.309 AC: 1074 AN: 3478

EpiCase AF: 0.359

EpiControl AF: 0.358

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.0010
DANN	Benign	0.28
DEOGEN2	Benign	0.096	T;.;T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.014	N
MetaRNN	Benign	0.0000028	T;T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.46	N;.;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.020	N;N;N
REVEL	Benign	0.21
Sift	Benign	0.98	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.028
MPC		0.18
ClinPred		0.00059	T
GERP RS		-5.0
Varity_R		0.023
gMVP		0.37

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: rs2295852; hg19: chr6-35923246; COSMIC: COSV62884916; COSMIC: COSV62884916;