rs1275719887

Variant names:

• chr3-52813453-C-A
• rs1275719887
• NM_002218.5:c.2761G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-52813453-C-A
• chr3-52813453-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002218.5(ITIH4):​c.2761G>T​(p.Val921Leu) 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. 15/21 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: 31)
• Consequence: ITIH4 NM_002218.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

Genes affected

ITIH4 (HGNC:6169): (inter-alpha-trypsin inhibitor heavy chain 4) The protein encoded by this gene is secreted into the blood, where it is cleaved by plasma kallikrein into two smaller forms. Expression of this gene has been detected only in liver, and it seems to be upregulated during surgical trauma. This gene is part of a cluster of similar genes on chromosome 3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ENSG00000243696 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06188503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITIH4	NM_002218.5	c.2761G>T	p.Val921Leu	missense_variant	Exon 24 of 24	ENST00000266041.9	NP_002209.2
ITIH4	NM_001166449.2	c.2671G>T	p.Val891Leu	missense_variant	Exon 22 of 22		NP_001159921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITIH4	ENST00000266041.9	c.2761G>T	p.Val921Leu	missense_variant	Exon 24 of 24	1	NM_002218.5	ENSP00000266041.4
ENSG00000243696	ENST00000468472.1	n.*4397G>T		non_coding_transcript_exon_variant	Exon 24 of 24	2		ENSP00000422253.1
ENSG00000243696	ENST00000468472.1	n.*4397G>T		3_prime_UTR_variant	Exon 24 of 24	2		ENSP00000422253.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000193 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.52
DANN	Benign	0.80
DEOGEN2	Benign	0.089	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.69	N;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.49	N;N;N
REVEL	Benign	0.013
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.029	B;B;.
Vest4		0.030
MutPred		0.48		.;Loss of glycosylation at P924 (P = 0.0972);.;
MVP		0.19
MPC		0.34
ClinPred		0.17	T
GERP RS		-2.5
Varity_R		0.046
gMVP		0.14

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: rs1275719887; hg19: chr3-52847469;