rs3821831

Variant names:

• chr3-52819385-C-T
• rs3821831
• ENST00000468472.1:n.*2599G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000468472.1(ENSG00000243696):​n.*2599G>A variant causes a non coding transcript exon 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. 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: ENSG00000243696 ENST00000468472.1 non_coding_transcript_exon
• Scores: Splicing: ADA: 0.00007385
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.86
• Publications: 20 publications found

Genes affected

ENSG00000243696 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ITIH4	NM_002218.5	c.2077+8G>A		splice_region_variant, intron_variant	Intron 17 of 23	ENST00000266041.9	NP_002209.2
ITIH4	NM_001166449.2	c.1987+8G>A		splice_region_variant, intron_variant	Intron 15 of 21		NP_001159921.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000243696	ENST00000468472.1	n.*2599G>A		non_coding_transcript_exon_variant	Exon 20 of 24	2		ENSP00000422253.1
ENSG00000243696	ENST00000468472.1	n.*2599G>A		3_prime_UTR_variant	Exon 20 of 24	2		ENSP00000422253.1
ITIH4	ENST00000266041.9	c.2077+8G>A		splice_region_variant, intron_variant	Intron 17 of 23	1	NM_002218.5	ENSP00000266041.4

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43892 AN: 152040 Hom.: 7021 Cov.: 33

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

GnomAD2 exomes AF: 0.291 AC: 73103 AN: 250812 AF XY: 0.298

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 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.: 37 AF XY: 0.347 AC XY: 252402 AN XY: 726896

African (AFR) AF: 0.180 AC: 6015 AN: 33466

American (AMR) AF: 0.170 AC: 7617 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 8234 AN: 26124

East Asian (EAS) AF: 0.0688 AC: 2729 AN: 39694

South Asian (SAS) AF: 0.274 AC: 23618 AN: 86246

European-Finnish (FIN) AF: 0.346 AC: 18474 AN: 53338

Middle Eastern (MID) AF: 0.360 AC: 2071 AN: 5756

European-Non Finnish (NFE) AF: 0.379 AC: 421397 AN: 1111516

Other (OTH) AF: 0.330 AC: 19915 AN: 60346

GnomAD4 genome AF: 0.288 AC: 43890 AN: 152158 Hom.: 7022 Cov.: 33 AF XY: 0.284 AC XY: 21120 AN XY: 74388

African (AFR) AF: 0.185 AC: 7692 AN: 41514

American (AMR) AF: 0.228 AC: 3488 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3466

East Asian (EAS) AF: 0.0776 AC: 402 AN: 5182

South Asian (SAS) AF: 0.256 AC: 1236 AN: 4826

European-Finnish (FIN) AF: 0.345 AC: 3660 AN: 10596

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25409 AN: 67962

Other (OTH) AF: 0.290 AC: 614 AN: 2114

Alfa AF: 0.341 Hom.: 33872

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

Submissions by phenotype

Hypercholesterolemia, susceptibility to Benign:1

Jan 01, 2004

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.037
DANN	Benign	0.62
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3821831; hg19: chr3-52853401; COSMIC: COSV56571513; COSMIC: COSV56571513;