Variant rs2276817 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002218.5(ITIH4):c.390G>A(p.Val130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,613,872 control chromosomes in the GnomAD database, including 47,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.25 ( 4842 hom., cov: 32)

Exomes 𝑓: 0.23 ( 42633 hom. )

Consequence

ITIH4
NM_002218.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0210

Variant links:

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]

ITIH4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 3-52826920-C-T is Benign according to our data. Variant chr3-52826920-C-T is described in ClinVar as [Benign]. Clinvar id is 3060681.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.021 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITIH4	NM_002218.5 linkuse as main transcript	c.390G>A	p.Val130=	synonymous_variant	4/24	ENST00000266041.9
ITIH4	NM_001166449.2 linkuse as main transcript	c.390G>A	p.Val130=	synonymous_variant	4/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITIH4	ENST00000266041.9 linkuse as main transcript	c.390G>A	p.Val130=	synonymous_variant	4/24	1	NM_002218.5	P2	Q14624-1

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37278

AN:

151960

Hom.:

4841

Cov.:

show subpopulations

Gnomad AFR

AF:

0.208

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.374

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.320

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.234

Gnomad OTH

AF:

0.243

GnomAD3 exomes

AF:

0.262

AC:

65839

AN:

251380

Hom.:

9951

AF XY:

0.248

AC XY:

33734

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.473

Gnomad ASJ exome

AF:

0.315

Gnomad EAS exome

AF:

0.309

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.231

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.234

AC:

342172

AN:

1461794

Hom.:

42633

Cov.:

AF XY:

0.230

AC XY:

167258

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.201

Gnomad4 AMR exome

AF:

0.458

Gnomad4 ASJ exome

AF:

0.321

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.119

Gnomad4 FIN exome

AF:

0.256

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.245

AC:

37299

AN:

152078

Hom.:

4842

Cov.:

AF XY:

0.247

AC XY:

18362

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.208

Gnomad4 AMR

AF:

0.374

Gnomad4 ASJ

AF:

0.313

Gnomad4 EAS

AF:

0.320

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.234

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.244

Hom.:

6205

Bravo

AF:

0.256

Asia WGS

AF:

0.237

AC:

822

AN:

3478

EpiCase

AF:

0.237

EpiControl

AF:

0.230

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ITIH4-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

7.2

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over