7-151066522-A-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 3P and 6B. PM2 PP2 BP4_Strong BP6_Moderate

The NM_003040.4(SLC4A2):c.584A>C(p.Gln195Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 35)
• Consequence: SLC4A2 NM_003040.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.05

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 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=0.050795794).
• BP6: Variant 7-151066522-A-C is Benign according to our data. Variant chr7-151066522-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2324967.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC4A2	NM_003040.4	c.584A>C	p.Gln195Pro	missense_variant	6/23	ENST00000413384.7
SLC4A2	NM_001199692.3	c.584A>C	p.Gln195Pro	missense_variant	6/23
SLC4A2	NM_001199693.1	c.557A>C	p.Gln186Pro	missense_variant	5/22
SLC4A2	NM_001199694.2	c.542A>C	p.Gln181Pro	missense_variant	5/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC4A2	ENST00000413384.7	c.584A>C	p.Gln195Pro	missense_variant	6/23	1	NM_003040.4	P1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 45

GnomAD4 genome Cov.: 35

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2022

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	0.050
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	0.027
Dann	Benign	0.67
DEOGEN2	Benign	0.049	T;T;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.015	N
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.051	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.020	N;N;N;N
REVEL	Benign	0.099
Sift	Benign	0.30	T;T;T;T
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.058
MutPred		0.12		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;.;
MVP		0.28
MPC		0.61
ClinPred		0.087	T
GERP RS		-9.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.085
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-150763609;