rs932650

chr10-113587600-T-Cchr10-113587600-T-G

Variant summary

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

The NM_004132.5(HABP2):c.1519-605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 152,020 control chromosomes in the GnomAD database, including 10,144 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 0.36 (10144 hom., cov: 32)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.538

Genes affected

HABP2 (HGNC:4798): (hyaluronan binding protein 2) This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_004132.5	c.1519-605T>C		intron_variant		ENST00000351270.4
HABP2	NM_001177660.3	c.1441-605T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000351270.4	c.1519-605T>C		intron_variant		1	NM_004132.5	P1
HABP2	ENST00000542051.5	c.1441-605T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54868 AN: 151902 Hom.: 10128 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.361 AC: 54927 AN: 152020 Hom.: 10144 Cov.: 32 AF XY: 0.359 AC XY: 26702 AN XY: 74306

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.318

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.355

Alfa AF: 0.346 Hom.: 14598

Bravo AF: 0.373

Asia WGS AF: 0.323 AC: 1121 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.55
Dann	Benign	0.28

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: rs932650; hg19: chr10-115347359;