rs569517338

Variant names:

• chr10-113589192-C-T
• rs569517338
• NM_004132.5:c.*823C>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.*823C>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 0.0000887 in 789,474 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 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000094 (0 hom.)
• Consequence: HABP2 NM_004132.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.312
• 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=-0.82).
• BS2: High AC in GnomAd4 at 10 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.*823C>T		3_prime_UTR	Exon 13 of 13	NP_004123.1	Q14520-1
	NRAP	NM_198060.4	MANE Select	c.5089-113G>A		intron	N/A	NP_932326.2
	HABP2	NM_001177660.3		c.*823C>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.*823C>T		3_prime_UTR	Exon 13 of 13	ENSP00000277903.4	Q14520-1
	NRAP	ENST00000359988.4	TSL:1 MANE Select	c.5089-113G>A		intron	N/A	ENSP00000353078.3	Q86VF7-1
	NRAP	ENST00000369358.8	TSL:1	c.5089-110G>A		intron	N/A	ENSP00000358365.4	A0A0A0MRM2

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152202 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: 0.00192

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: 0.0000942 AC: 60 AN: 637154 Hom.: 0 Cov.: 9 AF XY: 0.0000907 AC XY: 30 AN XY: 330580

African (AFR) AF: 0.00 AC: 0 AN: 16274

American (AMR) AF: 0.00 AC: 0 AN: 22640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15534

East Asian (EAS) AF: 0.00174 AC: 57 AN: 32670

South Asian (SAS) AF: 0.0000192 AC: 1 AN: 51988

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2390

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 427756

Other (OTH) AF: 0.0000615 AC: 2 AN: 32500

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152320 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74486

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

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

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000185

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	-0.82
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs569517338; hg19: chr10-115348951;