rs10885476

Variant names:

• chr10-113570962-G-A
• rs10885476
• NM_004132.5:c.107-3327G>A

Variant summary

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

The NM_004132.5(HABP2):​c.107-3327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,184 control chromosomes in the GnomAD database, including 1,643 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 0.14 (1643 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HABP2	NM_004132.5	c.107-3327G>A		intron_variant	Intron 2 of 12	ENST00000351270.4	NP_004123.1
HABP2	NM_001177660.3	c.29-3327G>A		intron_variant	Intron 2 of 12		NP_001171131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HABP2	ENST00000351270.4	c.107-3327G>A		intron_variant	Intron 2 of 12	1	NM_004132.5	ENSP00000277903.4
HABP2	ENST00000542051.5	c.29-3327G>A		intron_variant	Intron 2 of 12	2		ENSP00000443283.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21841 AN: 152066 Hom.: 1640 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0817

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.144 AC: 21853 AN: 152184 Hom.: 1643 Cov.: 33 AF XY: 0.141 AC XY: 10474 AN XY: 74406

African (AFR) AF: 0.117 AC: 4875 AN: 41518

American (AMR) AF: 0.126 AC: 1927 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 820 AN: 3466

East Asian (EAS) AF: 0.0820 AC: 425 AN: 5180

South Asian (SAS) AF: 0.129 AC: 620 AN: 4820

European-Finnish (FIN) AF: 0.145 AC: 1531 AN: 10582

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11097 AN: 68000

Other (OTH) AF: 0.140 AC: 296 AN: 2114

Alfa AF: 0.156 Hom.: 6138

Bravo AF: 0.140

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.53
PhyloP100		0.073
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: rs10885476; hg19: chr10-115330721;