rs2535633

Positions:

• chr3-52825614-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002218.5(ITIH4):​c.759+272G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,930 control chromosomes in the GnomAD database, including 18,644 homozygotes. 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: 𝑓 0.48 (18644 hom., cov: 32)
• Consequence: ITIH4 NM_002218.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITIH4	NM_002218.5	c.759+272G>C		intron_variant		ENST00000266041.9	NP_002209.2
ITIH4	NM_001166449.2	c.759+272G>C		intron_variant			NP_001159921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITIH4	ENST00000266041.9	c.759+272G>C		intron_variant		1	NM_002218.5	ENSP00000266041.4
ENSG00000243696	ENST00000468472.1	n.*891+272G>C		intron_variant		2		ENSP00000422253.1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72747 AN: 151812 Hom.: 18621 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.453

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.479 AC: 72822 AN: 151930 Hom.: 18644 Cov.: 32 AF XY: 0.477 AC XY: 35446 AN XY: 74266

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.454

Alfa AF: 0.447 Hom.: 2002

Bravo AF: 0.503

Asia WGS AF: 0.446 AC: 1548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.1
DANN	Benign	0.29

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: rs2535633; hg19: chr3-52859630;