Variant rs3617 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002217.4(ITIH3):c.943C>A(p.Gln315Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 1,612,218 control chromosomes in the GnomAD database, including 179,023 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.53 ( 22824 hom., cov: 33)

Exomes 𝑓: 0.46 ( 156199 hom. )

Consequence

ITIH3
NM_002217.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.771

Variant links:

Genes affected

ITIH3 (HGNC:6168): (inter-alpha-trypsin inhibitor heavy chain 3) This gene encodes the heavy chain subunit of the pre-alpha-trypsin inhibitor complex. This complex may stabilize the extracellular matrix through its ability to bind hyaluronic acid. Polymorphisms of this gene may be associated with increased risk for schizophrenia and major depressive disorder. This gene is present in an inter-alpha-trypsin inhibitor family gene cluster on chromosome 3. [provided by RefSeq, Jul 2015]

ITIH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.9009592E-6).

BP6

Variant 3-52799789-C-A is Benign according to our data. Variant chr3-52799789-C-A is described in ClinVar as [Benign]. Clinvar id is 1279402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITIH3	NM_002217.4 linkuse as main transcript	c.943C>A	p.Gln315Lys	missense_variant	9/22	ENST00000449956.3	NP_002208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITIH3	ENST00000449956.3 linkuse as main transcript	c.943C>A	p.Gln315Lys	missense_variant	9/22	1	NM_002217.4	ENSP00000415769	P1	Q06033-1

Frequencies

GnomAD3 genomes

AF:

0.535

AC:

81217

AN:

151912

Hom.:

22790

Cov.:

show subpopulations

Gnomad AFR

AF:

0.712

Gnomad AMI

AF:

0.534

Gnomad AMR

AF:

0.580

Gnomad ASJ

AF:

0.490

Gnomad EAS

AF:

0.420

Gnomad SAS

AF:

0.351

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.511

GnomAD3 exomes

AF:

0.479

AC:

118451

AN:

247344

Hom.:

29448

AF XY:

0.466

AC XY:

62521

AN XY:

134148

show subpopulations

Gnomad AFR exome

AF:

0.718

Gnomad AMR exome

AF:

0.608

Gnomad ASJ exome

AF:

0.486

Gnomad EAS exome

AF:

0.408

Gnomad SAS exome

AF:

0.346

Gnomad FIN exome

AF:

0.440

Gnomad NFE exome

AF:

0.462

Gnomad OTH exome

AF:

0.463

GnomAD4 exome

AF:

0.459

AC:

669504

AN:

1460190

Hom.:

156199

Cov.:

AF XY:

0.454

AC XY:

329916

AN XY:

726328

show subpopulations

Gnomad4 AFR exome

AF:

0.718

Gnomad4 AMR exome

AF:

0.602

Gnomad4 ASJ exome

AF:

0.495

Gnomad4 EAS exome

AF:

0.458

Gnomad4 SAS exome

AF:

0.344

Gnomad4 FIN exome

AF:

0.437

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.456

GnomAD4 genome

AF:

0.535

AC:

81309

AN:

152028

Hom.:

22824

Cov.:

AF XY:

0.531

AC XY:

39453

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.712

Gnomad4 AMR

AF:

0.580

Gnomad4 ASJ

AF:

0.490

Gnomad4 EAS

AF:

0.420

Gnomad4 SAS

AF:

0.351

Gnomad4 FIN

AF:

0.424

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.513

Alfa

AF:

0.474

Hom.:

42033

Bravo

AF:

0.557

TwinsUK

AF:

0.451

AC:

1671

ALSPAC

AF:

0.450

AC:

1733

ESP6500AA

AF:

0.710

AC:

2690

ESP6500EA

AF:

0.466

AC:

3852

ExAC

AF:

0.479

AC:

57829

Asia WGS

AF:

0.448

AC:

1555

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 32712163) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.7

DANN

Benign

0.46

DEOGEN2

Benign

0.0035

T;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.018

T;T;T

MetaRNN

Benign

0.0000019

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.8

.;.;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.32

PROVEAN

Benign

1.5

.;N;N

REVEL

Benign

0.18

Sift

Benign

0.43

.;T;T

Sift4G

Benign

0.97

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.043

MPC

0.13

ClinPred

0.0051

GERP RS

4.2

Varity_R

0.11

gMVP

0.34

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over