10-113589182-C-T

Variant names:

• chr10-113589182-C-T
• rs529487369
• NM_004132.5:c.*813C>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.*813C>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 0.000797 in 856,998 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (1 hom.)
• Consequence: HABP2 NM_004132.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.180
• 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=-0.83).
• BS2: High AC in GnomAd4 at 142 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.*813C>T		3_prime_UTR	Exon 13 of 13	NP_004123.1	Q14520-1
	NRAP	NM_198060.4	MANE Select	c.5089-103G>A		intron	N/A	NP_932326.2
	HABP2	NM_001177660.3		c.*813C>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.*813C>T		3_prime_UTR	Exon 13 of 13	ENSP00000277903.4	Q14520-1
	NRAP	ENST00000359988.4	TSL:1 MANE Select	c.5089-103G>A		intron	N/A	ENSP00000353078.3	Q86VF7-1
	NRAP	ENST00000369358.8	TSL:1	c.5089-100G>A		intron	N/A	ENSP00000358365.4	A0A0A0MRM2

Frequencies

GnomAD3 genomes AF: 0.000934 AC: 142 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00831

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000768 AC: 541 AN: 704774 Hom.: 1 Cov.: 9 AF XY: 0.000728 AC XY: 266 AN XY: 365532

African (AFR) AF: 0.0000556 AC: 1 AN: 17972

American (AMR) AF: 0.0000367 AC: 1 AN: 27244

Ashkenazi Jewish (ASJ) AF: 0.000833 AC: 14 AN: 16800

East Asian (EAS) AF: 0.00 AC: 0 AN: 33858

South Asian (SAS) AF: 0.00 AC: 0 AN: 56416

European-Finnish (FIN) AF: 0.00667 AC: 256 AN: 38404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2566

European-Non Finnish (NFE) AF: 0.000535 AC: 255 AN: 476746

Other (OTH) AF: 0.000403 AC: 14 AN: 34768

GnomAD4 genome AF: 0.000933 AC: 142 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.00126 AC XY: 94 AN XY: 74430

African (AFR) AF: 0.0000482 AC: 2 AN: 41536

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

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

European-Finnish (FIN) AF: 0.00831 AC: 88 AN: 10594

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

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68020

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00191 Hom.: 0

Bravo AF: 0.000196

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	-0.83
CADD	Benign	0.94
DANN	Benign	0.50
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism

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: rs529487369; hg19: chr10-115348941;