Variant 3-52818122-A-G 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.2226T>C(p.Ser742=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,613,456 control chromosomes in the GnomAD database, including 7,530 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 2796 hom., cov: 33)

Exomes 𝑓: 0.024 ( 4734 hom. )

Consequence

ITIH4
NM_002218.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.14

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=-0.89).

BP6

Variant 3-52818122-A-G is Benign according to our data. Variant chr3-52818122-A-G is described in ClinVar as [Benign]. Clinvar id is 3059195.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITIH4	NM_002218.5 linkuse as main transcript	c.2226T>C	p.Ser742=	synonymous_variant	20/24	ENST00000266041.9	NP_002209.2
ITIH4	NM_001166449.2 linkuse as main transcript	c.2136T>C	p.Ser712=	synonymous_variant	18/22		NP_001159921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITIH4	ENST00000266041.9 linkuse as main transcript	c.2226T>C	p.Ser742=	synonymous_variant	20/24	1	NM_002218.5	ENSP00000266041	P2	Q14624-1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16578

AN:

151878

Hom.:

2786

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.0114

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.0000947

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00128

Gnomad OTH

AF:

0.0657

GnomAD3 exomes

AF:

0.0543

AC:

13564

AN:

249914

Hom.:

1914

AF XY:

0.0575

AC XY:

7788

AN XY:

135414

show subpopulations

Gnomad AFR exome

AF:

0.363

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.00270

Gnomad EAS exome

AF:

0.0123

Gnomad SAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0239

AC:

34959

AN:

1461460

Hom.:

4734

Cov.:

AF XY:

0.0283

AC XY:

20551

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.0177

Gnomad4 ASJ exome

AF:

0.00268

Gnomad4 EAS exome

AF:

0.00877

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000645

Gnomad4 OTH exome

AF:

0.0378

GnomAD4 genome

AF:

0.109

AC:

16609

AN:

151996

Hom.:

2796

Cov.:

AF XY:

0.109

AC XY:

8124

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.355

Gnomad4 AMR

AF:

0.0382

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.0115

Gnomad4 SAS

AF:

0.209

Gnomad4 FIN

AF:

0.0000947

Gnomad4 NFE

AF:

0.00128

Gnomad4 OTH

AF:

0.0655

Alfa

AF:

0.0357

Hom.:

424

Bravo

AF:

0.119

Asia WGS

AF:

0.126

AC:

438

AN:

3478

EpiCase

AF:

0.00153

EpiControl

AF:

0.00213

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

Nov 06, 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

-0.89

CADD

Benign

0.45

DANN

Benign

0.72

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

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