10-113567929-T-C

Position:

• chr10-113567929-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+404T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.668 in 151,968 control chromosomes in the GnomAD database, including 34,424 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 0.67 (34424 hom., cov: 32)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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]

HABP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HABP2	NM_004132.5	c.106+404T>C		intron_variant		ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.28+404T>C		intron_variant			NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.106+404T>C		intron_variant		1	NM_004132.5	ENSP00000277903.4
HABP2	ENST00000542051.5	c.28+404T>C		intron_variant		2		ENSP00000443283.1
HABP2	ENST00000460714.1	n.42+404T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.668 AC: 101487 AN: 151850 Hom.: 34402 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.792

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.665

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

GnomAD4 genome AF: 0.668 AC: 101551 AN: 151968 Hom.: 34424 Cov.: 32 AF XY: 0.674 AC XY: 50046 AN XY: 74268

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.735

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.792

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.669

Alfa AF: 0.678 Hom.: 6623

Bravo AF: 0.666

Asia WGS AF: 0.807 AC: 2805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.65

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: rs3862018; hg19: chr10-115327688;