rs3862019

Variant names:

• chr10-113569191-T-C
• rs3862019
• NM_004132.5:c.106+1666T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HABP2	NM_004132.5	c.106+1666T>C		intron_variant	Intron 2 of 12	ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.28+1666T>C		intron_variant	Intron 2 of 12		NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.106+1666T>C		intron_variant	Intron 2 of 12	1	NM_004132.5	ENSP00000277903.4
HABP2	ENST00000542051.5	c.28+1666T>C		intron_variant	Intron 2 of 12	2		ENSP00000443283.1
HABP2	ENST00000460714.1	n.43-453T>C		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.346 AC: 14339 AN: 41468

American (AMR) AF: 0.687 AC: 10501 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2355 AN: 3470

East Asian (EAS) AF: 0.823 AC: 4249 AN: 5160

South Asian (SAS) AF: 0.759 AC: 3660 AN: 4822

European-Finnish (FIN) AF: 0.650 AC: 6874 AN: 10574

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.643 AC: 43694 AN: 67964

Other (OTH) AF: 0.609 AC: 1283 AN: 2108

Alfa AF: 0.620 Hom.: 42543

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
PhyloP100		-4.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3862019; hg19: chr10-115328950;