7-151062007-G-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC4A2 NM_003040.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• hereditary spherocytosis type 4

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• osteopetrosis, autosomal recessive 9

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia

LOC128092247 (HGNC:0):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003040.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	NM_003040.4	MANE Select	c.20G>C	p.Arg7Pro	missense	Exon 2 of 23	NP_003031.3
	SLC4A2	NM_001199692.3		c.20G>C	p.Arg7Pro	missense	Exon 2 of 23	NP_001186621.1	P04920-1
	LOC128092247	NM_001414898.1	MANE Select	c.*29G>C		downstream_gene	N/A	NP_001401827.1	A0A6Q8PFQ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.20G>C	p.Arg7Pro	missense	Exon 2 of 23	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.20G>C	p.Arg7Pro	missense	Exon 2 of 23	ENSP00000419412.1
	SLC4A2	ENST00000490898.5	TSL:3	c.20G>C	p.Arg7Pro	missense	Exon 2 of 5	ENSP00000418114.1	C9J9M9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.027
Eigen_PC	Benign	0.040
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.67	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	-0.34	N
PhyloP100		1.4
PrimateAI	Benign	0.46	T
PROVEAN	Benign	1.5	N
REVEL	Benign	0.16
Sift	Benign	0.081	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.83	P
Vest4		0.50
MutPred		0.34		Loss of MoRF binding (P = 2e-04)
MVP		0.56
MPC		1.6
ClinPred		0.85	D
GERP RS		4.7
PromoterAI		0.0065	Neutral
Varity_R		0.26
gMVP		0.42
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs747989506; hg19: chr7-150759094;