NM_004132.5:c.70-6750C>T

Variant names:

• chr10-113560739-C-T
• rs7093962
• NM_004132.5:c.70-6750C>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.70-6750C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.965 in 152,300 control chromosomes in the GnomAD database, including 71,000 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 0.97 (71000 hom., cov: 33)
• Consequence: HABP2 NM_004132.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.984 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.70-6750C>T		intron	N/A	NP_004123.1
	HABP2	NM_001177660.3		c.-9-6750C>T		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.70-6750C>T		intron	N/A	ENSP00000277903.4
	HABP2	ENST00000883707.1		c.70-6750C>T		intron	N/A	ENSP00000553766.1
	HABP2	ENST00000542051.5	TSL:2	c.-9-6750C>T		intron	N/A	ENSP00000443283.1

Frequencies

GnomAD3 genomes AF: 0.965 AC: 146875 AN: 152182 Hom.: 70955 Cov.: 33

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.982

Gnomad ASJ AF: 0.961

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.990

Gnomad OTH AF: 0.967

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

GnomAD4 genome AF: 0.965 AC: 146974 AN: 152300 Hom.: 71000 Cov.: 33 AF XY: 0.965 AC XY: 71870 AN XY: 74468

African (AFR) AF: 0.909 AC: 37764 AN: 41550

American (AMR) AF: 0.982 AC: 15031 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 3338 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5177 AN: 5178

South Asian (SAS) AF: 0.977 AC: 4715 AN: 4824

European-Finnish (FIN) AF: 0.975 AC: 10346 AN: 10606

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.990 AC: 67380 AN: 68044

Other (OTH) AF: 0.967 AC: 2045 AN: 2114

Alfa AF: 0.981 Hom.: 89299

Bravo AF: 0.963

Asia WGS AF: 0.982 AC: 3415 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		0.043
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: rs7093962; hg19: chr10-115320498;