10-113567312-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004132.5(HABP2):​c.70-177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0651 in 152,178 control chromosomes in the GnomAD database, including 381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.065 ( 381 hom., cov: 33)

Consequence

HABP2
NM_004132.5 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.23
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 10-113567312-G-A is Benign according to our data. Variant chr10-113567312-G-A is described in ClinVar as [Benign]. Clinvar id is 1275964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HABP2NM_004132.5 linkuse as main transcriptc.70-177G>A intron_variant ENST00000351270.4
HABP2NM_001177660.3 linkuse as main transcriptc.-9-177G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HABP2ENST00000351270.4 linkuse as main transcriptc.70-177G>A intron_variant 1 NM_004132.5 P1Q14520-1
HABP2ENST00000542051.5 linkuse as main transcriptc.-9-177G>A intron_variant 2 Q14520-2

Frequencies

GnomAD3 genomes
AF:
0.0651
AC:
9900
AN:
152060
Hom.:
379
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0372
Gnomad AMI
AF:
0.0899
Gnomad AMR
AF:
0.0565
Gnomad ASJ
AF:
0.0677
Gnomad EAS
AF:
0.0424
Gnomad SAS
AF:
0.110
Gnomad FIN
AF:
0.0300
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.0869
Gnomad OTH
AF:
0.0798
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0651
AC:
9907
AN:
152178
Hom.:
381
Cov.:
33
AF XY:
0.0636
AC XY:
4731
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0373
Gnomad4 AMR
AF:
0.0564
Gnomad4 ASJ
AF:
0.0677
Gnomad4 EAS
AF:
0.0423
Gnomad4 SAS
AF:
0.110
Gnomad4 FIN
AF:
0.0300
Gnomad4 NFE
AF:
0.0869
Gnomad4 OTH
AF:
0.0804
Alfa
AF:
0.0250
Hom.:
10
Bravo
AF:
0.0671

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJan 10, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.045
DANN
Benign
0.54

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

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

Other links and lift over

dbSNP: rs11575667; hg19: chr10-115327071; COSMIC: COSV63635969; COSMIC: COSV63635969; API