rs2710322

chr3-52783577-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002215.4(ITIH1):c.1225+238T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,208 control chromosomes in the GnomAD database, including 56,917 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.86 (56917 hom., cov: 32)
• Consequence: ITIH1 NM_002215.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

Genes affected

ITIH1 (HGNC:6166): (inter-alpha-trypsin inhibitor heavy chain 1) This gene encodes a member of the inter-alpha-trypsin inhibitor family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate the heavy chain of the inter-alpha-trypsin inhibitor complex, which is secreted by hepatocytes into the blood. The heavy chain also interacts with hyaluronan, and this interaction may play a role in ovulation and fertilization, and has been implicated in multiple inflammatory diseases. This gene is present in a gene cluster on chromosome 3. [provided by RefSeq, Nov 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITIH1	NM_002215.4	c.1225+238T>C		intron_variant		ENST00000273283.7
ITIH1	NM_001166434.3	c.799+238T>C		intron_variant
ITIH1	NM_001166435.2	c.361+238T>C		intron_variant
ITIH1	NM_001166436.2	c.361+238T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITIH1	ENST00000273283.7	c.1225+238T>C		intron_variant		1	NM_002215.4	P1
ITIH1	ENST00000537050.5	c.361+238T>C		intron_variant		2
ITIH1	ENST00000628722.2	n.1080+238T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131323 AN: 152090 Hom.: 56872 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.856

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.728

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.875

Gnomad OTH AF: 0.854

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.863 AC: 131423 AN: 152208 Hom.: 56917 Cov.: 32 AF XY: 0.860 AC XY: 64005 AN XY: 74422

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.894

Gnomad4 NFE AF: 0.875

Gnomad4 OTH AF: 0.854

Alfa AF: 0.865 Hom.: 36341

Bravo AF: 0.862

Asia WGS AF: 0.713 AC: 2481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.26
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs2710322; hg19: chr3-52817593;