Variant 4-71255295-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2

The NM_001098484.3(SLC4A4):c.149G>C(p.Gly50Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,613,320 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 8 hom. )

Consequence

SLC4A4
NM_001098484.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 7.35

Variant links:

Genes affected

SLC4A4 (HGNC:11030): (solute carrier family 4 member 4) This gene encodes a sodium bicarbonate cotransporter (NBC) involved in the regulation of bicarbonate secretion and absorption and intracellular pH. Mutations in this gene are associated with proximal renal tubular acidosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

SLC4A4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC4A4. . Gene score misZ 3.144 (greater than the threshold 3.09). Trascript score misZ 4.3739 (greater than threshold 3.09). GenCC has associacion of gene with autosomal recessive proximal renal tubular acidosis.

BP4

Computational evidence support a benign effect (MetaRNN=0.0113144815).

BS2

High Homozygotes in GnomAdExome4 at 8 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC4A4	NM_001098484.3 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	3/26	ENST00000264485.11	NP_001091954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A4	ENST00000264485.11 linkuse as main transcript	c.149G>C	p.Gly50Ala	missense_variant	3/26	1	NM_001098484.3	ENSP00000264485	P3	Q9Y6R1-1

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

151888

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000702

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00297

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00157

AC:

390

AN:

249120

Hom.:

AF XY:

0.00152

AC XY:

205

AN XY:

135138

show subpopulations

Gnomad AFR exome

AF:

0.000711

Gnomad AMR exome

AF:

0.000580

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000789

Gnomad NFE exome

AF:

0.00289

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.00268

AC:

3914

AN:

1461312

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

1860

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.000651

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00327

Gnomad4 OTH exome

AF:

0.00232

GnomAD4 genome

AF:

0.00176

AC:

267

AN:

152008

Hom.:

Cov.:

AF XY:

0.00148

AC XY:

110

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000700

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.00296

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00241

Hom.:

Bravo

AF:

0.00184

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000516

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00157

AC:

190

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00191

EpiControl

AF:

0.00267

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mendelics

May 04, 2022

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.37

T;T;.;.;.;.

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

.;D;D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Benign

0.011

T;T;T;T;T;T

MetaSVM

Benign

-0.47

MutationAssessor

Benign

1.8

L;L;L;L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

.;N;N;N;.;.

REVEL

Benign

0.29

Sift

Benign

0.26

.;T;T;T;.;.

Sift4G

Uncertain

0.016

.;D;D;D;.;.

Polyphen

0.034

B;B;.;P;.;.

Vest4

0.26, 0.27, 0.28

MVP

0.41

MPC

0.60

ClinPred

0.042

GERP RS

5.7

Varity_R

0.25

gMVP

0.30

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

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