NM_004132.5:c.*765C>G

Variant names:

• chr10-113589134-C-G
• rs886046747
• NM_004132.5:c.*765C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004132.5(HABP2):​c.*765C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000764 in 1,308,322 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: HABP2 NM_004132.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 0 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]

NRAP (HGNC:7988): (nebulin related anchoring protein) Predicted to enable actin filament binding activity and muscle alpha-actinin binding activity. Predicted to be involved in cardiac muscle thin filament assembly. Predicted to be located in fascia adherens; muscle tendon junction; and myofibril. Predicted to be active in Z disc. [provided by Alliance of Genome Resources, Apr 2022]

NRAP Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HABP2	NM_004132.5	MANE Select	c.*765C>G		3_prime_UTR	Exon 13 of 13	NP_004123.1	Q14520-1
	NRAP	NM_198060.4	MANE Select	c.5089-55G>C		intron	N/A	NP_932326.2
	HABP2	NM_001177660.3		c.*765C>G		3_prime_UTR	Exon 13 of 13	NP_001171131.1	Q14520-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HABP2	ENST00000351270.4	TSL:1 MANE Select	c.*765C>G		3_prime_UTR	Exon 13 of 13	ENSP00000277903.4	Q14520-1
	NRAP	ENST00000359988.4	TSL:1 MANE Select	c.5089-55G>C		intron	N/A	ENSP00000353078.3	Q86VF7-1
	NRAP	ENST00000369358.8	TSL:1	c.5089-52G>C		intron	N/A	ENSP00000358365.4	A0A0A0MRM2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.64e-7 AC: 1 AN: 1308322 Hom.: 0 Cov.: 19 AF XY: 0.00000152 AC XY: 1 AN XY: 657224

African (AFR) AF: 0.00 AC: 0 AN: 30388

American (AMR) AF: 0.00 AC: 0 AN: 43694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24522

East Asian (EAS) AF: 0.00 AC: 0 AN: 38984

South Asian (SAS) AF: 0.00 AC: 0 AN: 81688

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4338

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 979450

Other (OTH) AF: 0.00 AC: 0 AN: 55142

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.63
DANN	Benign	0.48
PhyloP100		-0.55

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: rs886046747; hg19: chr10-115348893;