rs1889524

chr10-7575504-G-A

Variant summary

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

The NM_030569.7(ITIH5):c.1978+949C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,972 control chromosomes in the GnomAD database, including 21,133 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 0.52 (21133 hom., cov: 31)
• Consequence: ITIH5 NM_030569.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865

Genes affected

ITIH5 (HGNC:21449): (inter-alpha-trypsin inhibitor heavy chain 5) This gene encodes a heavy chain component of one of the inter-alpha-trypsin inhibitor (ITI) family members. ITI proteins are involved in extracellular matrix stabilization and in the prevention of tumor metastasis. They are also structurally related plasma serine protease inhibitors and are composed of a light chain and varying numbers of heavy chains. This family member is thought to function as a tumor suppressor in breast and thyroid cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITIH5	NM_030569.7	c.1978+949C>T		intron_variant		ENST00000397146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITIH5	ENST00000397146.7	c.1978+949C>T		intron_variant		1	NM_030569.7	P1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79542 AN: 151854 Hom.: 21127 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.524 AC: 79591 AN: 151972 Hom.: 21133 Cov.: 31 AF XY: 0.529 AC XY: 39271 AN XY: 74278

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.498

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.537

Gnomad4 OTH AF: 0.500

Alfa AF: 0.525 Hom.: 3579

Bravo AF: 0.519

Asia WGS AF: 0.602 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.033
Dann	Benign	0.44

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: rs1889524; hg19: chr10-7617467;