10-113560739-C-T

Position:

• chr10-113560739-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004132.5(HABP2):​c.70-6750C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 152,300 control chromosomes in the GnomAD database, including 71,000 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 0.97 (71000 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HABP2	NM_004132.5	c.70-6750C>T		intron_variant		ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.-9-6750C>T		intron_variant			NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.70-6750C>T		intron_variant		1	NM_004132.5	ENSP00000277903.4
HABP2	ENST00000542051.5	c.-9-6750C>T		intron_variant		2		ENSP00000443283.1

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146875 AN: 152182 Hom.: 70955 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.967

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

GnomAD4 genome AF: 0.965 AC: 146974 AN: 152300 Hom.: 71000 Cov.: 33 AF XY: 0.965 AC XY: 71870 AN XY: 74468

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.982

Gnomad4 ASJ AF: 0.961

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.977

Gnomad4 FIN AF: 0.975

Gnomad4 NFE AF: 0.990

Gnomad4 OTH AF: 0.967

Alfa AF: 0.984 Hom.: 67780

Bravo AF: 0.963

Asia WGS AF: 0.982 AC: 3415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.68

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: rs7093962; hg19: chr10-115320498;