10-113567186-G-A

Position:

• chr10-113567186-G-A

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.70-303G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,012 control chromosomes in the GnomAD database, including 3,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (3261 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0540

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=-0.93).
• BP6: Variant 10-113567186-G-A is Benign according to our data. Variant chr10-113567186-G-A is described in ClinVar as [Benign]. Clinvar id is 1297834.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HABP2	NM_004132.5	c.70-303G>A		intron_variant		ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.-9-303G>A		intron_variant			NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.70-303G>A		intron_variant		1	NM_004132.5	ENSP00000277903	P1
HABP2	ENST00000542051.5	c.-9-303G>A		intron_variant		2		ENSP00000443283

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27994 AN: 151888 Hom.: 3250 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.184 AC: 28023 AN: 152012 Hom.: 3261 Cov.: 33 AF XY: 0.193 AC XY: 14304 AN XY: 74296

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.195

Alfa AF: 0.174 Hom.: 333

Bravo AF: 0.199

Asia WGS AF: 0.334 AC: 1159 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	-0.93
CADD	Benign	0.099
DANN	Benign	0.60

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: rs11196380; hg19: chr10-115326945;