rs2240878

Positions:

• chr10-113553584-C-A
• chr10-113553584-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.69+394C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,132 control chromosomes in the GnomAD database, including 8,068 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 0.32 (8068 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_004132.5	c.69+394C>A		intron_variant		ENST00000351270.4
HABP2	NM_001177660.3	c.-10+2623C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000351270.4	c.69+394C>A		intron_variant		1	NM_004132.5	P1
HABP2	ENST00000542051.5	c.-10+2623C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48879 AN: 152014 Hom.: 8066 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.321 AC: 48893 AN: 152132 Hom.: 8068 Cov.: 33 AF XY: 0.324 AC XY: 24086 AN XY: 74346

Gnomad4 AFR AF: 0.328

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.406

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.363

Alfa AF: 0.260 Hom.: 1315

Bravo AF: 0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.32

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: rs2240878; hg19: chr10-115313343;