rs1537631

chr10-7575796-A-Gchr10-7575796-A-T

Variant summary

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

The NM_030569.7(ITIH5):c.1978+657T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,010 control chromosomes in the GnomAD database, including 20,369 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 0.51 (20369 hom., cov: 32)
• Consequence: ITIH5 NM_030569.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITIH5	NM_030569.7	c.1978+657T>C		intron_variant		ENST00000397146.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITIH5	ENST00000397146.7	c.1978+657T>C		intron_variant		1	NM_030569.7	P1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77769 AN: 151892 Hom.: 20361 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.512 AC: 77816 AN: 152010 Hom.: 20369 Cov.: 32 AF XY: 0.518 AC XY: 38516 AN XY: 74302

Gnomad4 AFR AF: 0.411

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.538

Gnomad4 OTH AF: 0.495

Alfa AF: 0.528 Hom.: 10177

Bravo AF: 0.506

Asia WGS AF: 0.604 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	2.4
Dann	Benign	0.45

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: rs1537631; hg19: chr10-7617759;