10-113567191-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004132.5(HABP2):c.70-298C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,858 control chromosomes in the GnomAD database, including 7,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7282 hom., cov: 32)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 10-113567191-C-G is Benign according to our data. Variant chr10-113567191-C-G is described in ClinVar as [Benign]. Clinvar id is 1270510.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_004132.5	c.70-298C>G		intron_variant		ENST00000351270.4
HABP2	NM_001177660.3	c.-9-298C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000351270.4	c.70-298C>G		intron_variant		1	NM_004132.5	P1
HABP2	ENST00000542051.5	c.-9-298C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45346 AN: 151736 Hom.: 7262 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.299 AC: 45399 AN: 151858 Hom.: 7282 Cov.: 32 AF XY: 0.303 AC XY: 22524 AN XY: 74216

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.307

Alfa AF: 0.273 Hom.: 802

Bravo AF: 0.324

Asia WGS AF: 0.413 AC: 1436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.95
Cadd	Benign	0.091
Dann	Benign	0.54

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: rs10885475; hg19: chr10-115326950;