rs2302373

Positions:

• chr10-113583528-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004132.5(HABP2):​c.1237+170C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 151,988 control chromosomes in the GnomAD database, including 32,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.65 (32135 hom., cov: 32)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.716

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 10-113583528-C-T is Benign according to our data. Variant chr10-113583528-C-T is described in ClinVar as [Benign]. Clinvar id is 1291252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HABP2	NM_004132.5	c.1237+170C>T		intron_variant		ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.1159+170C>T		intron_variant			NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.1237+170C>T		intron_variant		1	NM_004132.5	ENSP00000277903	P1
HABP2	ENST00000542051.5	c.1159+170C>T		intron_variant		2		ENSP00000443283

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98100 AN: 151870 Hom.: 32096 Cov.: 32

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.522

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.646 AC: 98189 AN: 151988 Hom.: 32135 Cov.: 32 AF XY: 0.642 AC XY: 47709 AN XY: 74288

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.522

Gnomad4 EAS AF: 0.748

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.662

Alfa AF: 0.613 Hom.: 59492

Bravo AF: 0.665

Asia WGS AF: 0.684 AC: 2378 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.53
DANN	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2302373; hg19: chr10-115343287;