rs2535629

Positions:

• chr3-52799203-G-A
• chr3-52799203-G-C

Variant summary

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

The NM_002217.4(ITIH3):​c.789+112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,380,636 control chromosomes in the GnomAD database, including 97,334 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 0.45 (17354 hom., cov: 33)
  • Exomes 𝑓: 0.35 (79980 hom.)
• Consequence: ITIH3 NM_002217.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITIH3	NM_002217.4	c.789+112G>A		intron_variant		ENST00000449956.3	NP_002208.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITIH3	ENST00000449956.3	c.789+112G>A		intron_variant		1	NM_002217.4	ENSP00000415769	P1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68989 AN: 151988 Hom.: 17325 Cov.: 33

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.353 AC: 433425 AN: 1228530 Hom.: 79980 Cov.: 17 AF XY: 0.349 AC XY: 213158 AN XY: 610212

Gnomad4 AFR exome AF: 0.693

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.393

Gnomad4 EAS exome AF: 0.419

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.336

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.454 AC: 69070 AN: 152106 Hom.: 17354 Cov.: 33 AF XY: 0.453 AC XY: 33717 AN XY: 74390

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.414

Alfa AF: 0.370 Hom.: 8141

Bravo AF: 0.475

Asia WGS AF: 0.378 AC: 1313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.61
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2535629; hg19: chr3-52833219;