rs10885476

chr10-113570962-G-A

Variant summary

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

The NM_004132.5(HABP2):c.107-3327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,184 control chromosomes in the GnomAD database, including 1,643 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 0.14 (1643 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_004132.5	c.107-3327G>A		intron_variant		ENST00000351270.4
HABP2	NM_001177660.3	c.29-3327G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000351270.4	c.107-3327G>A		intron_variant		1	NM_004132.5	P1
HABP2	ENST00000542051.5	c.29-3327G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21841 AN: 152066 Hom.: 1640 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.144 AC: 21853 AN: 152184 Hom.: 1643 Cov.: 33 AF XY: 0.141 AC XY: 10474 AN XY: 74406

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0820

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.140

Alfa AF: 0.160 Hom.: 2734

Bravo AF: 0.140

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.3
Dann	Benign	0.53

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: rs10885476; hg19: chr10-115330721;