Variant rs7084817 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002216.3(ITIH2):c.1705C>G(p.Leu569Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0469 in 1,613,892 control chromosomes in the GnomAD database, including 2,016 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.035 ( 121 hom., cov: 32)

Exomes 𝑓: 0.048 ( 1895 hom. )

Consequence

ITIH2
NM_002216.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

ITIH2 (HGNC:6167): (inter-alpha-trypsin inhibitor heavy chain 2) The inter-alpha-trypsin inhibitors (ITI) are a family of structurally related plasma serine protease inhibitors involved in extracellular matrix stabilization and in prevention of tumor metastasis. The ITI family contains multiple proteins made up of a light chain (see MIM 176870) and a variable number of heavy chains (Salier et al., 1987 [PubMed 2446322]; Himmelfarb et al., 2004 [PubMed 14744536]).[supplied by OMIM, Nov 2009]

ITIH2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033824742).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITIH2	NM_002216.3 linkuse as main transcript	c.1705C>G	p.Leu569Val	missense_variant	14/21	ENST00000358415.9	NP_002207.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ITIH2	ENST00000358415.9 linkuse as main transcript	c.1705C>G	p.Leu569Val	missense_variant	14/21	1	NM_002216.3	ENSP00000351190	P1
ITIH2	ENST00000379587.4 linkuse as main transcript	c.1672C>G	p.Leu558Val	missense_variant	13/20	5		ENSP00000368906
ITIH2	ENST00000477751.1 linkuse as main transcript	n.513C>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0355

AC:

5398

AN:

152148

Hom.:

121

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0130

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0245

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.00674

Gnomad SAS

AF:

0.0419

Gnomad FIN

AF:

0.0591

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0498

Gnomad OTH

AF:

0.0301

GnomAD3 exomes

AF:

0.0404

AC:

10167

AN:

251434

Hom.:

275

AF XY:

0.0424

AC XY:

5761

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.0116

Gnomad AMR exome

AF:

0.0168

Gnomad ASJ exome

AF:

0.0327

Gnomad EAS exome

AF:

0.0104

Gnomad SAS exome

AF:

0.0454

Gnomad FIN exome

AF:

0.0656

Gnomad NFE exome

AF:

0.0511

Gnomad OTH exome

AF:

0.0415

GnomAD4 exome

AF:

0.0480

AC:

70230

AN:

1461626

Hom.:

1895

Cov.:

AF XY:

0.0484

AC XY:

35212

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.0109

Gnomad4 AMR exome

AF:

0.0172

Gnomad4 ASJ exome

AF:

0.0336

Gnomad4 EAS exome

AF:

0.00433

Gnomad4 SAS exome

AF:

0.0478

Gnomad4 FIN exome

AF:

0.0630

Gnomad4 NFE exome

AF:

0.0516

Gnomad4 OTH exome

AF:

0.0456

GnomAD4 genome

AF:

0.0355

AC:

5399

AN:

152266

Hom.:

121

Cov.:

AF XY:

0.0350

AC XY:

2607

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.0244

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.00676

Gnomad4 SAS

AF:

0.0423

Gnomad4 FIN

AF:

0.0591

Gnomad4 NFE

AF:

0.0498

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0471

Hom.:

133

Bravo

AF:

0.0312

TwinsUK

AF:

0.0523

AC:

194

ALSPAC

AF:

0.0524

AC:

202

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.0497

AC:

427

ExAC

AF:

0.0405

AC:

4915

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0514

EpiControl

AF:

0.0512

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

0.92

D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.057

Sift

Benign

0.032

D;D

Sift4G

Benign

0.10

T;T

Polyphen

0.98

D;.

Vest4

0.22

MPC

0.32

ClinPred

0.017

GERP RS

3.5

Varity_R

0.15

gMVP

0.74

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over