rs3862019

Positions:

• chr10-113569191-T-C

Variant summary

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

The NM_004132.5(HABP2):​c.106+1666T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 152,056 control chromosomes in the GnomAD database, including 26,961 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 0.58 (26961 hom., cov: 32)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.45

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 (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HABP2	NM_004132.5	c.106+1666T>C		intron_variant		ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.28+1666T>C		intron_variant			NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.106+1666T>C		intron_variant		1	NM_004132.5	ENSP00000277903.4
HABP2	ENST00000542051.5	c.28+1666T>C		intron_variant		2		ENSP00000443283.1
HABP2	ENST00000460714.1	n.43-453T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87614 AN: 151938 Hom.: 26947 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.824

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.577 AC: 87675 AN: 152056 Hom.: 26961 Cov.: 32 AF XY: 0.584 AC XY: 43426 AN XY: 74324

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.823

Gnomad4 SAS AF: 0.759

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.609

Alfa AF: 0.627 Hom.: 29325

Bravo AF: 0.567

Asia WGS AF: 0.753 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.029
DANN	Benign	0.41

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: rs3862019; hg19: chr10-115328950;