3-52801338-C-T

Variant names:

• chr3-52801338-C-T
• rs736408
• NM_002217.4:c.1383+192C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 54 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002217.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITIH3	NM_002217.4	MANE Select	c.1383+192C>T		intron	N/A	NP_002208.3	Q06033-1
	ITIH3	NM_001392019.1		c.1383+192C>T		intron	N/A	NP_001378948.1	A0A994J439
	ITIH3	NM_001392020.1		c.1383+192C>T		intron	N/A	NP_001378949.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITIH3	ENST00000449956.3	TSL:1 MANE Select	c.1383+192C>T		intron	N/A	ENSP00000415769.2	Q06033-1
	ITIH3	ENST00000703834.1		c.1383+192C>T		intron	N/A	ENSP00000515492.1	A0A994J439
	ITIH3	ENST00000889655.1		c.1383+192C>T		intron	N/A	ENSP00000559714.1

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

African (AFR) AF: 0.684 AC: 28376 AN: 41506

American (AMR) AF: 0.482 AC: 7367 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1328 AN: 3472

East Asian (EAS) AF: 0.379 AC: 1961 AN: 5174

South Asian (SAS) AF: 0.312 AC: 1504 AN: 4820

European-Finnish (FIN) AF: 0.372 AC: 3935 AN: 10576

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24145 AN: 67982

Other (OTH) AF: 0.419 AC: 885 AN: 2112

Alfa AF: 0.401 Hom.: 33834

Bravo AF: 0.480

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.44
PhyloP100		-0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs736408; hg19: chr3-52835354;