rs1885436

Variant names:

• chr10-113577779-C-G
• rs1885436
• NM_004132.5:c.449-247C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004132.5(HABP2):​c.449-247C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.819 in 152,196 control chromosomes in the GnomAD database, including 51,162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.82 (51162 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.272
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 10-113577779-C-G is Benign according to our data. Variant chr10-113577779-C-G is described in ClinVar as Benign. ClinVar VariationId is 1288592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.919 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.449-247C>G		intron	N/A	NP_004123.1
	HABP2	NM_001177660.3		c.371-247C>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.449-247C>G		intron	N/A	ENSP00000277903.4
	HABP2	ENST00000542051.5	TSL:2	c.371-247C>G		intron	N/A	ENSP00000443283.1

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124553 AN: 152078 Hom.: 51105 Cov.: 33

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.940

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.771

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.819 AC: 124672 AN: 152196 Hom.: 51162 Cov.: 33 AF XY: 0.817 AC XY: 60797 AN XY: 74406

African (AFR) AF: 0.800 AC: 33210 AN: 41510

American (AMR) AF: 0.856 AC: 13099 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2721 AN: 3472

East Asian (EAS) AF: 0.941 AC: 4869 AN: 5176

South Asian (SAS) AF: 0.819 AC: 3952 AN: 4826

European-Finnish (FIN) AF: 0.771 AC: 8166 AN: 10596

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55964 AN: 68000

Other (OTH) AF: 0.838 AC: 1771 AN: 2114

Alfa AF: 0.812 Hom.: 6211

Bravo AF: 0.828

Asia WGS AF: 0.866 AC: 3013 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-0.27
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: rs1885436; hg19: chr10-115337538;