Variant 3-52819385-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002218.5(ITIH4):c.2077+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,613,340 control chromosomes in the GnomAD database, including 100,256 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.29 ( 7022 hom., cov: 33)

Exomes 𝑓: 0.35 ( 93234 hom. )

Consequence

ITIH4
NM_002218.5 splice_region, intron

Scores

Splicing: ADA: 0.00007385

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.86

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 3-52819385-C-T is Benign according to our data. Variant chr3-52819385-C-T is described in ClinVar as [Benign]. Clinvar id is 9042.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.37 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.2077+8G>A		splice_region_variant, intron_variant		ENST00000266041.9	NP_002209.2
ITIH4	NM_001166449.2 linkuse as main transcript	c.1987+8G>A		splice_region_variant, intron_variant			NP_001159921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITIH4	ENST00000266041.9 linkuse as main transcript	c.2077+8G>A		splice_region_variant, intron_variant		1	NM_002218.5	ENSP00000266041	P2	Q14624-1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43892

AN:

152040

Hom.:

7021

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.214

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.0776

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.291

AC:

73103

AN:

250812

Hom.:

11935

AF XY:

0.298

AC XY:

40433

AN XY:

135576

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.314

Gnomad EAS exome

AF:

0.0734

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.341

Gnomad NFE exome

AF:

0.377

Gnomad OTH exome

AF:

0.317

GnomAD4 exome

AF:

0.349

AC:

510070

AN:

1461182

Hom.:

93234

Cov.:

AF XY:

0.347

AC XY:

252402

AN XY:

726896

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.170

Gnomad4 ASJ exome

AF:

0.315

Gnomad4 EAS exome

AF:

0.0688

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.346

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.330

GnomAD4 genome

AF:

0.288

AC:

43890

AN:

152158

Hom.:

7022

Cov.:

AF XY:

0.284

AC XY:

21120

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.228

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.0776

Gnomad4 SAS

AF:

0.256

Gnomad4 FIN

AF:

0.345

Gnomad4 NFE

AF:

0.374

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.348

Hom.:

16891

Bravo

AF:

0.272

Asia WGS

AF:

0.165

AC:

577

AN:

3478

EpiCase

AF:

0.370

EpiControl

AF:

0.373

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hypercholesterolemia, susceptibility to

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jan 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.037

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000074

dbscSNV1_RF

Benign

0.016

SpliceAI score (max)

0.030

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