rs3781387

Positions:

• chr10-113557893-A-G
• chr10-113557893-A-T

Variant summary

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

The ENST00000351270.4(HABP2):​c.69+4703A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,260 control chromosomes in the GnomAD database, including 3,193 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 0.18 (3193 hom., cov: 33)
• Consequence: HABP2 ENST00000351270.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.518

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HABP2	NM_004132.5	c.69+4703A>G		intron_variant		ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.-10+6932A>G		intron_variant			NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.69+4703A>G		intron_variant		1	NM_004132.5	ENSP00000277903	P1
HABP2	ENST00000542051.5	c.-10+6932A>G		intron_variant		2		ENSP00000443283

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27077 AN: 152140 Hom.: 3182 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.178 AC: 27116 AN: 152260 Hom.: 3193 Cov.: 33 AF XY: 0.181 AC XY: 13474 AN XY: 74440

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.199

Alfa AF: 0.182 Hom.: 626

Bravo AF: 0.202

Asia WGS AF: 0.316 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.62

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: rs3781387; hg19: chr10-115317652;