NM_003040.4:c.162C>G

Variant names:

• chr7-151064312-C-G
• rs371330147
• NM_003040.4:c.162C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003040.4(SLC4A2):​c.162C>G​(p.Ala54Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000779 in 1,283,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A54A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: SLC4A2 NM_003040.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.92
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-5.92 with no splicing effect.

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.162C>G	p.Ala54Ala	synonymous	Exon 3 of 23	NP_003031.3
	SLC4A2	NM_001199692.3		c.162C>G	p.Ala54Ala	synonymous	Exon 3 of 23	NP_001186621.1	P04920-1
	SLC4A2	NM_001199693.1		c.135C>G	p.Ala45Ala	synonymous	Exon 2 of 22	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.162C>G	p.Ala54Ala	synonymous	Exon 3 of 23	ENSP00000405600.2	P04920-1
	SLC4A2	ENST00000485713.6	TSL:1	c.162C>G	p.Ala54Ala	synonymous	Exon 3 of 23	ENSP00000419412.1
	SLC4A2	ENST00000461735.1	TSL:1	c.120C>G	p.Ala40Ala	synonymous	Exon 2 of 22	ENSP00000419164.1	P04920-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 7.79e-7 AC: 1 AN: 1283272 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 636004

African (AFR) AF: 0.00 AC: 0 AN: 28596

American (AMR) AF: 0.00 AC: 0 AN: 39438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19698

East Asian (EAS) AF: 0.00 AC: 0 AN: 23450

South Asian (SAS) AF: 0.00 AC: 0 AN: 84592

European-Finnish (FIN) AF: 0.0000266 AC: 1 AN: 37618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3566

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 997600

Other (OTH) AF: 0.00 AC: 0 AN: 48714

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.74
DANN	Benign	0.70
PhyloP100		-5.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs371330147; hg19: chr7-150761399;