rs2240878

Variant names:

• chr10-113553584-C-A
• rs2240878
• NM_004132.5:c.69+394C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-113553584-C-A
• chr10-113553584-C-T

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+394C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,132 control chromosomes in the GnomAD database, including 8,068 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 0.32 (8068 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.45 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+394C>A		intron	N/A	NP_004123.1
	HABP2	NM_001177660.3		c.-10+2623C>A		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+394C>A		intron	N/A	ENSP00000277903.4
	HABP2	ENST00000542051.5	TSL:2	c.-10+2623C>A		intron	N/A	ENSP00000443283.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48879 AN: 152014 Hom.: 8066 Cov.: 33

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.321 AC: 48893 AN: 152132 Hom.: 8068 Cov.: 33 AF XY: 0.324 AC XY: 24086 AN XY: 74346

African (AFR) AF: 0.328 AC: 13619 AN: 41502

American (AMR) AF: 0.289 AC: 4416 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3470

East Asian (EAS) AF: 0.176 AC: 911 AN: 5176

South Asian (SAS) AF: 0.466 AC: 2246 AN: 4818

European-Finnish (FIN) AF: 0.299 AC: 3160 AN: 10572

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21895 AN: 68000

Other (OTH) AF: 0.363 AC: 765 AN: 2106

Alfa AF: 0.284 Hom.: 2539

Bravo AF: 0.312

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.32
PhyloP100		-0.026
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: rs2240878; hg19: chr10-115313343;