7-151068149-G-C

Variant names:

• chr7-151068149-G-C
• rs12703112
• NM_003040.4:c.1147+95G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003040.4(SLC4A2):​c.1147+95G>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC4A2 NM_003040.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395
• Publications: 5 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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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.1147+95G>C		intron	N/A	NP_003031.3
	SLC4A2	NM_001199692.3		c.1147+95G>C		intron	N/A	NP_001186621.1	P04920-1
	SLC4A2	NM_001199693.1		c.1120+95G>C		intron	N/A	NP_001186622.1	Q59GF1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC4A2	ENST00000413384.7	TSL:1 MANE Select	c.1147+95G>C		intron	N/A	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.1147+95G>C		intron	N/A	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.1105+95G>C		intron	N/A	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 810610 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 400536

African (AFR) AF: 0.00 AC: 0 AN: 16666

American (AMR) AF: 0.00 AC: 0 AN: 9984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14962

East Asian (EAS) AF: 0.00 AC: 0 AN: 26438

South Asian (SAS) AF: 0.00 AC: 0 AN: 40628

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2972

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 630642

Other (OTH) AF: 0.00 AC: 0 AN: 37314

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 3178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.63
PhyloP100		-0.40

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: rs12703112; hg19: chr7-150765236;