10-113567281-A-G

Variant summary

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

The NM_004132.5(HABP2):c.70-208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0653 in 152,200 control chromosomes in the GnomAD database, including 380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.065 (380 hom., cov: 32)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.235

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=-0.97).
• BP6: Variant 10-113567281-A-G is Benign according to our data. Variant chr10-113567281-A-G is described in ClinVar as [Benign]. Clinvar id is 1253107.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HABP2	NM_004132.5	c.70-208A>G		intron_variant		ENST00000351270.4
HABP2	NM_001177660.3	c.-9-208A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000351270.4	c.70-208A>G		intron_variant		1	NM_004132.5	P1
HABP2	ENST00000542051.5	c.-9-208A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0653 AC: 9926 AN: 152082 Hom.: 378 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0671

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0297

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0870

Gnomad OTH AF: 0.0802

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

GnomAD4 genome AF: 0.0653 AC: 9933 AN: 152200 Hom.: 380 Cov.: 32 AF XY: 0.0637 AC XY: 4742 AN XY: 74416

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0671

Gnomad4 EAS AF: 0.0423

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0297

Gnomad4 NFE AF: 0.0869

Gnomad4 OTH AF: 0.0808

Alfa AF: 0.0379 Hom.: 24

Bravo AF: 0.0673

Asia WGS AF: 0.0680 AC: 236 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	-0.97
Cadd	Benign	4.2
Dann	Benign	0.38

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: rs11575665; hg19: chr10-115327040; COSMIC: COSV63635964; COSMIC: COSV63635964;