7-151062007-G-C

Variant names:

• chr7-151062007-G-C
• rs747989506
• NM_003040.4:c.20G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003040.4(SLC4A2):​c.20G>C​(p.Arg7Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC4A2 NM_003040.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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]

ENSG00000288608 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19803217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC4A2	NM_003040.4	c.20G>C	p.Arg7Pro	missense_variant	Exon 2 of 23	ENST00000413384.7	NP_003031.3
SLC4A2	NM_001199692.3	c.20G>C	p.Arg7Pro	missense_variant	Exon 2 of 23		NP_001186621.1
LOC128092247	NM_001414898.1	c.*29G>C		downstream_gene_variant			NP_001401827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC4A2	ENST00000413384.7	c.20G>C	p.Arg7Pro	missense_variant	Exon 2 of 23	1	NM_003040.4	ENSP00000405600.2
ENSG00000288608	ENST00000674552.1	c.*29G>C		downstream_gene_variant				ENSP00000501917.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0026	T;T;T;T;.;.;.
Eigen	Benign	-0.027
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.67	T;.;T;T;T;T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	-0.34	.;N;N;.;.;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	1.5	N;N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.081	T;T;T;T;T;T;T
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		0.83	.;P;P;.;.;.;.
Vest4		0.50, 0.50
MutPred		0.34		Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP		0.56
MPC		1.6
ClinPred		0.85	D
GERP RS		4.7
Varity_R		0.26
gMVP		0.42

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

Other links and lift over

dbSNP: rs747989506; hg19: chr7-150759094;