10-113553052-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001177660.3(HABP2):c.-10+2091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,067,296 control chromosomes in the GnomAD database, including 65,312 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8406 hom., cov: 33)
  • Exomes 𝑓: 0.34 (56906 hom.)
• Consequence: HABP2 NM_001177660.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.84

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-113553052-T-C is Benign according to our data. Variant chr10-113553052-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 298892.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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_001177660.3	c.-10+2091T>C		intron_variant
HABP2	NM_004132.5			upstream_gene_variant		ENST00000351270.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HABP2	ENST00000542051.5	c.-10+2091T>C		intron_variant		2
HABP2	ENST00000351270.4			upstream_gene_variant		1	NM_004132.5	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50035 AN: 151808 Hom.: 8401 Cov.: 33

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.375

GnomAD4 exome AF: 0.343 AC: 314105 AN: 915368 Hom.: 56906 Cov.: 12 AF XY: 0.351 AC XY: 166516 AN XY: 474072

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.224

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.222

Gnomad4 SAS exome AF: 0.474

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.355

GnomAD4 genome AF: 0.330 AC: 50064 AN: 151928 Hom.: 8406 Cov.: 33 AF XY: 0.331 AC XY: 24575 AN XY: 74256

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.408

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.466

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.371

Alfa AF: 0.341 Hom.: 4534

Bravo AF: 0.319

Asia WGS AF: 0.317 AC: 1103 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

Factor VII Marburg I Variant Thrombophilia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.7
Dann	Benign	0.80

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: rs2240879; hg19: chr10-115312811; COSMIC: COSV63636221;