10-113567434-A-G

Position:

• chr10-113567434-A-G

Variant summary

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

The ENST00000351270.4(HABP2):​c.70-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 1,378,492 control chromosomes in the GnomAD database, including 85,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7827 hom., cov: 33)
  • Exomes 𝑓: 0.35 (77775 hom.)
• Consequence: HABP2 ENST00000351270.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.56

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=-0.94).
• BP6: Variant 10-113567434-A-G is Benign according to our data. Variant chr10-113567434-A-G is described in ClinVar as [Benign]. Clinvar id is 1287963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HABP2	NM_004132.5	c.70-55A>G		intron_variant		ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.-9-55A>G		intron_variant			NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.70-55A>G		intron_variant		1	NM_004132.5	ENSP00000277903	P1
HABP2	ENST00000542051.5	c.-9-55A>G		intron_variant		2		ENSP00000443283
HABP2	ENST00000460714.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47422 AN: 152066 Hom.: 7830 Cov.: 33

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0992

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.346 AC: 424685 AN: 1226308 Hom.: 77775 Cov.: 18 AF XY: 0.343 AC XY: 213122 AN XY: 620954

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.314

Gnomad4 EAS exome AF: 0.0773

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.396

Gnomad4 NFE exome AF: 0.380

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.312 AC: 47426 AN: 152184 Hom.: 7827 Cov.: 33 AF XY: 0.307 AC XY: 22836 AN XY: 74404

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.0998

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.270

Alfa AF: 0.293 Hom.: 1515

Bravo AF: 0.295

Asia WGS AF: 0.186 AC: 649 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.97
DANN	Benign	0.23

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: rs2286745; hg19: chr10-115327193;