10-113567514-G-T

Position:

chr10-113567514-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004132.5(HABP2):c.95G>T(p.Ser32Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00676 in 1,612,156 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0070 ( 52 hom. )

Consequence

HABP2
NM_004132.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.563

Variant links:

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]

HABP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0056200027).

BP6

Variant 10-113567514-G-T is Benign according to our data. Variant chr10-113567514-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 298896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-113567514-G-T is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 689 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_004132.5 linkuse as main transcript	c.95G>T	p.Ser32Ile	missense_variant	2/13	ENST00000351270.4
HABP2	NM_001177660.3 linkuse as main transcript	c.17G>T	p.Ser6Ile	missense_variant	2/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000351270.4 linkuse as main transcript	c.95G>T	p.Ser32Ile	missense_variant	2/13	1	NM_004132.5	P1	Q14520-1
HABP2	ENST00000542051.5 linkuse as main transcript	c.17G>T	p.Ser6Ile	missense_variant	2/13	2			Q14520-2
HABP2	ENST00000460714.1 linkuse as main transcript	n.31G>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.00453

AC:

690

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00406

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00789

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00419

AC:

1054

AN:

251330

Hom.:

AF XY:

0.00434

AC XY:

590

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00492

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00711

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00700

AC:

10215

AN:

1459838

Hom.:

Cov.:

AF XY:

0.00677

AC XY:

4915

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00519

Gnomad4 ASJ exome

AF:

0.000804

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00855

Gnomad4 OTH exome

AF:

0.00628

GnomAD4 genome

AF:

0.00452

AC:

689

AN:

152318

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

285

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00789

Gnomad4 OTH

AF:

0.00663

Alfa

AF:

0.00733

Hom.:

Bravo

AF:

0.00484

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00895

AC:

ExAC

AF:

0.00381

AC:

463

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.00794

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jun 28, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	HABP2: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 01, 2021	This variant is associated with the following publications: (PMID: 28089742) -

Factor VII Marburg I Variant Thrombophilia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

4.0

DANN

Benign

0.66

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.0056

T;T

MetaSVM

Benign

-0.76

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.20

Sift

Benign

0.16

T;T

Sift4G

Benign

0.12

T;T

Polyphen

0.019

.;B

Vest4

0.24

MVP

0.32

MPC

0.0098

ClinPred

0.00091

GERP RS

0.46

Varity_R

0.044

gMVP

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over