chr7-151066534-C-T

Position:

chr7-151066534-C-T

Variant summary

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

The NM_003040.4(SLC4A2):c.596C>T(p.Ala199Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 1,503,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00015 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

SLC4A2
NM_003040.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0870

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:

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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=0.032219023).

BP6

Variant 7-151066534-C-T is Benign according to our data. Variant chr7-151066534-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3319954.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC4A2	NM_003040.4 linkuse as main transcript	c.596C>T	p.Ala199Val	missense_variant	6/23	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3 linkuse as main transcript	c.596C>T	p.Ala199Val	missense_variant	6/23		NP_001186621.1
SLC4A2	NM_001199693.1 linkuse as main transcript	c.569C>T	p.Ala190Val	missense_variant	5/22		NP_001186622.1
SLC4A2	NM_001199694.2 linkuse as main transcript	c.554C>T	p.Ala185Val	missense_variant	5/22		NP_001186623.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7 linkuse as main transcript	c.596C>T	p.Ala199Val	missense_variant	6/23	1	NM_003040.4	ENSP00000405600	P1	P04920-1

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

141506

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000675

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00649

Gnomad NFE

AF:

0.000236

Gnomad OTH

AF:

0.000505

GnomAD3 exomes

AF:

0.0000540

AC:

AN:

129532

Hom.:

AF XY:

0.0000439

AC XY:

AN XY:

68370

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:

0.000157

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000855

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000734

AC:

100

AN:

1362154

Hom.:

Cov.:

AF XY:

0.0000760

AC XY:

AN XY:

670896

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000309

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000794

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000797

Gnomad4 OTH exome

AF:

0.0000896

GnomAD4 genome

AF:

0.000148

AC:

AN:

141616

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

AN XY:

69458

show subpopulations

Gnomad4 AFR

AF:

0.0000315

Gnomad4 AMR

AF:

0.0000674

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000236

Gnomad4 OTH

AF:

0.000499

Alfa

AF:

0.000161

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000262

AC:

ExAC

AF:

0.0000138

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 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

0.079

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.6

DANN

Benign

0.96

DEOGEN2

Benign

0.063

T;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.48

.;T;T;T

M_CAP

Benign

0.066

MetaRNN

Benign

0.032

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

N;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.21

N;N;N;N

REVEL

Benign

0.13

Sift

Benign

0.41

T;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.037

MVP

0.20

MPC

0.49

ClinPred

0.074

GERP RS

-0.49

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.035

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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