rs736408

Positions:

• chr3-52801338-C-T

Variant summary

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

The NM_002217.4(ITIH3):​c.1383+192C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,124 control chromosomes in the GnomAD database, including 17,713 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 0.46 (17713 hom., cov: 33)
• Consequence: ITIH3 NM_002217.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITIH3	NM_002217.4	c.1383+192C>T		intron_variant		ENST00000449956.3	NP_002208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITIH3	ENST00000449956.3	c.1383+192C>T		intron_variant		1	NM_002217.4	ENSP00000415769	P1
ITIH3	ENST00000416872.6	c.1383+192C>T		intron_variant		2		ENSP00000413922
ITIH3	ENST00000703834.1	c.1383+192C>T		intron_variant				ENSP00000515492
ITIH3	ENST00000464804.1	n.460+192C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69974 AN: 152006 Hom.: 17685 Cov.: 33

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.461 AC: 70056 AN: 152124 Hom.: 17713 Cov.: 33 AF XY: 0.460 AC XY: 34214 AN XY: 74366

Gnomad4 AFR AF: 0.684

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.419

Alfa AF: 0.376 Hom.: 15168

Bravo AF: 0.480

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs736408; hg19: chr3-52835354;