2-232457036-T-C

Variant names:

• chr2-232457036-T-C
• rs3111341
• NM_001631.5:c.438T>C

Variant summary

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

The NM_001631.5(ALPI):​c.438T>C​(p.Asn146Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,260 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.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ALPI NM_001631.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.44
• Publications: 0 publications found

Genes affected

ALPI (HGNC:437): (alkaline phosphatase, intestinal) There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The intestinal alkaline phosphatase gene encodes a digestive brush-border enzyme. This enzyme is a component of the gut mucosal defense system and is thought to function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in the gut. [provided by RefSeq, Dec 2014]

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=-0.74).
• BP7: Synonymous conserved (PhyloP=-3.44 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001631.5. 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
	ALPI	NM_001631.5	MANE Select	c.438T>C	p.Asn146Asn	synonymous	Exon 4 of 11	NP_001622.2	P09923

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPI	ENST00000295463.4	TSL:1 MANE Select	c.438T>C	p.Asn146Asn	synonymous	Exon 4 of 11	ENSP00000295463.3	P09923
	ALPI	ENST00000457560.1	TSL:5	n.*367T>C		non_coding_transcript_exon	Exon 3 of 10	ENSP00000413068.1	F8WEQ0
	ALPI	ENST00000457560.1	TSL:5	n.*367T>C		3_prime_UTR	Exon 3 of 10	ENSP00000413068.1	F8WEQ0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461260 Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2 AN XY: 726944

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111994

Other (OTH) AF: 0.0000166 AC: 1 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.044
DANN	Benign	0.27
PhyloP100		-3.4
Mutation Taster		=100/0	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: rs3111341; hg19: chr2-233321746;