rs1889524

Variant names:

• chr10-7575504-G-A
• rs1889524
• NM_030569.7:c.1978+949C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ITIH5	NM_030569.7	c.1978+949C>T		intron_variant	Intron 10 of 13	ENST00000397146.7	NP_085046.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITIH5	ENST00000397146.7	c.1978+949C>T		intron_variant	Intron 10 of 13	1	NM_030569.7	ENSP00000380333.3

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

African (AFR) AF: 0.457 AC: 18911 AN: 41426

American (AMR) AF: 0.528 AC: 8072 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1729 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3992 AN: 5176

South Asian (SAS) AF: 0.543 AC: 2613 AN: 4816

European-Finnish (FIN) AF: 0.593 AC: 6253 AN: 10550

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.537 AC: 36469 AN: 67936

Other (OTH) AF: 0.500 AC: 1055 AN: 2112

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
PhyloP100		-0.86
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: rs1889524; hg19: chr10-7617467;