rs6585234

chr10-113570889-T-C

Variant summary

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

The NM_004132.5(HABP2):c.106+3364T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,092 control chromosomes in the GnomAD database, including 43,888 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 0.75 (43888 hom., cov: 32)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_004132.5	c.106+3364T>C		intron_variant		ENST00000351270.4
HABP2	NM_001177660.3	c.28+3364T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000351270.4	c.106+3364T>C		intron_variant		1	NM_004132.5	P1
HABP2	ENST00000542051.5	c.28+3364T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113786 AN: 151974 Hom.: 43857 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.941

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.826

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.749 AC: 113868 AN: 152092 Hom.: 43888 Cov.: 32 AF XY: 0.749 AC XY: 55670 AN XY: 74338

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.793

Gnomad4 EAS AF: 0.941

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.771

Gnomad4 NFE AF: 0.826

Gnomad4 OTH AF: 0.778

Alfa AF: 0.757 Hom.: 5933

Bravo AF: 0.748

Asia WGS AF: 0.848 AC: 2948 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	2.6
Dann	Benign	0.86

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: rs6585234; hg19: chr10-115330648;