chr10-113557893-A-G

Variant names:

• chr10-113557893-A-G
• rs3781387
• NM_004132.5:c.69+4703A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004132.5(HABP2):​c.69+4703A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,260 control chromosomes in the GnomAD database, including 3,193 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 0.18 (3193 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.518
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004132.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HABP2	NM_004132.5	MANE Select	c.69+4703A>G		intron	N/A	NP_004123.1
	HABP2	NM_001177660.3		c.-10+6932A>G		intron	N/A	NP_001171131.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HABP2	ENST00000351270.4	TSL:1 MANE Select	c.69+4703A>G		intron	N/A	ENSP00000277903.4
	HABP2	ENST00000542051.5	TSL:2	c.-10+6932A>G		intron	N/A	ENSP00000443283.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27077 AN: 152140 Hom.: 3182 Cov.: 33

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.178 AC: 27116 AN: 152260 Hom.: 3193 Cov.: 33 AF XY: 0.181 AC XY: 13474 AN XY: 74440

African (AFR) AF: 0.167 AC: 6942 AN: 41564

American (AMR) AF: 0.378 AC: 5784 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3470

East Asian (EAS) AF: 0.458 AC: 2373 AN: 5176

South Asian (SAS) AF: 0.136 AC: 654 AN: 4812

European-Finnish (FIN) AF: 0.143 AC: 1513 AN: 10602

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8848 AN: 68022

Other (OTH) AF: 0.199 AC: 419 AN: 2106

Alfa AF: 0.182 Hom.: 642

Bravo AF: 0.202

Asia WGS AF: 0.316 AC: 1095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.7
DANN	Benign	0.62
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3781387; hg19: chr10-115317652;