rs4918842

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004132.5(HABP2):​c.69+3863T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,090 control chromosomes in the GnomAD database, including 2,698 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2698 hom., cov: 31)

Consequence

HABP2
NM_004132.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.539
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HABP2NM_004132.5 linkuse as main transcriptc.69+3863T>C intron_variant ENST00000351270.4
HABP2NM_001177660.3 linkuse as main transcriptc.-10+6092T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HABP2ENST00000351270.4 linkuse as main transcriptc.69+3863T>C intron_variant 1 NM_004132.5 P1Q14520-1
HABP2ENST00000542051.5 linkuse as main transcriptc.-10+6092T>C intron_variant 2 Q14520-2

Frequencies

GnomAD3 genomes
AF:
0.156
AC:
23711
AN:
151972
Hom.:
2685
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0933
Gnomad AMI
AF:
0.0989
Gnomad AMR
AF:
0.369
Gnomad ASJ
AF:
0.127
Gnomad EAS
AF:
0.446
Gnomad SAS
AF:
0.135
Gnomad FIN
AF:
0.142
Gnomad MID
AF:
0.155
Gnomad NFE
AF:
0.130
Gnomad OTH
AF:
0.181
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.156
AC:
23746
AN:
152090
Hom.:
2698
Cov.:
31
AF XY:
0.159
AC XY:
11857
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0932
Gnomad4 AMR
AF:
0.370
Gnomad4 ASJ
AF:
0.127
Gnomad4 EAS
AF:
0.445
Gnomad4 SAS
AF:
0.136
Gnomad4 FIN
AF:
0.142
Gnomad4 NFE
AF:
0.130
Gnomad4 OTH
AF:
0.181
Alfa
AF:
0.143
Hom.:
2744
Bravo
AF:
0.178
Asia WGS
AF:
0.309
AC:
1074
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.85
DANN
Benign
0.33

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: rs4918842; hg19: chr10-115316812; API