NM_004132.5:c.*822C>T

Variant names:

• chr10-113589191-C-T
• rs551018573
• NM_004132.5:c.*822C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004132.5(HABP2):​c.*822C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000431 in 788,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: HABP2 NM_004132.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0590
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAdExome4 at 30 AD gene.

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.*822C>T		3_prime_UTR	Exon 13 of 13	NP_004123.1	Q14520-1
	NRAP	NM_198060.4	MANE Select	c.5089-112G>A		intron	N/A	NP_932326.2
	HABP2	NM_001177660.3		c.*822C>T		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.*822C>T		3_prime_UTR	Exon 13 of 13	ENSP00000277903.4	Q14520-1
	NRAP	ENST00000359988.4	TSL:1 MANE Select	c.5089-112G>A		intron	N/A	ENSP00000353078.3	Q86VF7-1
	NRAP	ENST00000369358.8	TSL:1	c.5089-109G>A		intron	N/A	ENSP00000358365.4	A0A0A0MRM2

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152156 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000472 AC: 30 AN: 635990 Hom.: 0 Cov.: 8 AF XY: 0.0000454 AC XY: 15 AN XY: 330086

African (AFR) AF: 0.00 AC: 0 AN: 16260

American (AMR) AF: 0.00 AC: 0 AN: 22626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15538

East Asian (EAS) AF: 0.000887 AC: 29 AN: 32692

South Asian (SAS) AF: 0.00 AC: 0 AN: 51962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2384

European-Non Finnish (NFE) AF: 0.00000234 AC: 1 AN: 426640

Other (OTH) AF: 0.00 AC: 0 AN: 32492

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152274 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74462

African (AFR) AF: 0.00 AC: 0 AN: 41550

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Factor VII Marburg I Variant Thrombophilia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.1
DANN	Benign	0.48
PhyloP100		-0.059

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: rs551018573; hg19: chr10-115348950;