chr10-113552847-G-A

Position:

• chr10-113552847-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001177660.3(HABP2):​c.-10+1886G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,214 control chromosomes in the GnomAD database, including 1,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1492 hom., cov: 33)
• Consequence: HABP2 NM_001177660.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.426

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 10-113552847-G-A is Benign according to our data. Variant chr10-113552847-G-A is described in ClinVar as [Benign]. Clinvar id is 1269429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HABP2	NM_001177660.3	c.-10+1886G>A		intron_variant			NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000542051.5	c.-10+1886G>A		intron_variant		2		ENSP00000443283

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18499 AN: 152096 Hom.: 1494 Cov.: 33

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0212

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.121 AC: 18489 AN: 152214 Hom.: 1492 Cov.: 33 AF XY: 0.121 AC XY: 9000 AN XY: 74406

Gnomad4 AFR AF: 0.0345

Gnomad4 AMR AF: 0.117

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.0213

Gnomad4 SAS AF: 0.0692

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.151

Alfa AF: 0.163 Hom.: 2165

Bravo AF: 0.111

Asia WGS AF: 0.0580 AC: 202 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2240880; hg19: chr10-115312606;