Variant chr8-91334332-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000276609.8(SLC26A7):c.680G>A(p.Arg227Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000868 in 1,612,756 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 1 hom. )

Consequence

SLC26A7
ENST00000276609.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.129

Variant links:

Genes affected

SLC26A7 (HGNC:14467): (solute carrier family 26 member 7) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. This gene has abundant and specific expression in the kidney. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Aug 2013]

SLC26A7 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03820789).

BP6

Variant 8-91334332-G-A is Benign according to our data. Variant chr8-91334332-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3319329.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC26A7	NM_052832.4 linkuse as main transcript	c.680G>A	p.Arg227Gln	missense_variant	6/19	ENST00000276609.8	NP_439897.1
SLC26A7	NM_134266.2 linkuse as main transcript	c.680G>A	p.Arg227Gln	missense_variant	6/19		NP_599028.1
SLC26A7	NM_001282356.2 linkuse as main transcript	c.680G>A	p.Arg227Gln	missense_variant	7/20		NP_001269285.1
SLC26A7	NM_001282357.2 linkuse as main transcript	c.-141G>A		5_prime_UTR_variant	7/19		NP_001269286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A7	ENST00000276609.8 linkuse as main transcript	c.680G>A	p.Arg227Gln	missense_variant	6/19	1	NM_052832.4	ENSP00000276609	P1	Q8TE54-1

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000140

AC:

AN:

250490

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.000349

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.0000707

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000712

AC:

104

AN:

1460500

Hom.:

Cov.:

AF XY:

0.0000826

AC XY:

AN XY:

726542

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000426

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.0000829

GnomAD4 genome

AF:

0.000236

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000763

Hom.:

Bravo

AF:

0.000181

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000179

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 17, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.30

CADD

Benign

9.9

DANN

Benign

0.97

DEOGEN2

Benign

0.35

T;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.81

.;T;.;T

M_CAP

Benign

0.031

MetaRNN

Benign

0.038

T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

-0.27

N;N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.54

N;.;N;N

REVEL

Benign

0.23

Sift

Benign

0.44

T;.;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.14

MVP

0.52

MPC

0.13

ClinPred

0.012

GERP RS

-0.49

Varity_R

0.045

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over