Variant 7-151066584-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_003040.4(SLC4A2):c.646G>A(p.Gly216Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000187 in 1,547,222 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SLC4A2
NM_003040.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.77

Variant links:

Genes affected

SLC4A2 (HGNC:11028): (solute carrier family 4 member 2) This gene encodes a member of the anion exchanger family of membrane transport proteins. The encoded protein regulates intracellular pH, biliary bicarbonate secretion, and chloride uptake. Reduced expression of this gene may be associated with primary biliary cirrhosis (PBC) in human patients, while differential expression of this gene may be associated with malignant hepatocellular carcinoma, colon and gastric cancers. [provided by RefSeq, Nov 2016]

SLC4A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, SLC4A2

BP4

Computational evidence support a benign effect (MetaRNN=0.25957763).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC4A2	NM_003040.4 linkuse as main transcript	c.646G>A	p.Gly216Arg	missense_variant	6/23	ENST00000413384.7
SLC4A2	NM_001199692.3 linkuse as main transcript	c.646G>A	p.Gly216Arg	missense_variant	6/23
SLC4A2	NM_001199693.1 linkuse as main transcript	c.619G>A	p.Gly207Arg	missense_variant	5/22
SLC4A2	NM_001199694.2 linkuse as main transcript	c.604G>A	p.Gly202Arg	missense_variant	5/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000413384.7 linkuse as main transcript	c.646G>A	p.Gly216Arg	missense_variant	6/23	1	NM_003040.4	P1	P04920-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

148266

Hom.:

AF XY:

0.0000126

AC XY:

AN XY:

79102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000545

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1395044

Hom.:

Cov.:

AF XY:

0.0000218

AC XY:

AN XY:

688068

show subpopulations

Gnomad4 AFR exome

AF:

0.0000635

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000213

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000263

AC:

ExAC

AF:

0.0000270

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Martin Pollak Laboratory, Beth Israel Deaconess Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

Cadd

Benign

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.087

T;T;.;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.85

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.26

T;T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

0.92

L;L;.;.

MutationTaster

Benign

0.63

D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.39

N;N;N;N

REVEL

Benign

0.28

Sift

Benign

0.59

T;T;T;T

Sift4G

Benign

0.38

T;T;T;T

Polyphen

1.0

D;D;.;D

Vest4

0.41

MutPred

0.23

Gain of methylation at G216 (P = 0.0097);Gain of methylation at G216 (P = 0.0097);.;.;

MVP

0.73

MPC

0.75

ClinPred

0.24

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.052

gMVP

0.41

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