rs557625429

Variant names:

• chr10-113588787-C-T
• rs557625429
• NM_198060.4:c.*188G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198060.4(NRAP):​c.*188G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 596,032 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 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: NRAP NM_198060.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.109
• Publications: 0 publications found

Genes affected

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]

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198060.4. 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
	NRAP	NM_198060.4	MANE Select	c.*188G>A		3_prime_UTR	Exon 42 of 42	NP_932326.2
	HABP2	NM_004132.5	MANE Select	c.*418C>T		3_prime_UTR	Exon 13 of 13	NP_004123.1	Q14520-1
	NRAP	NM_006175.5		c.*188G>A		3_prime_UTR	Exon 41 of 41	NP_006166.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRAP	ENST00000359988.4	TSL:1 MANE Select	c.*188G>A		3_prime_UTR	Exon 42 of 42	ENSP00000353078.3	Q86VF7-1
	HABP2	ENST00000351270.4	TSL:1 MANE Select	c.*418C>T		3_prime_UTR	Exon 13 of 13	ENSP00000277903.4	Q14520-1
	NRAP	ENST00000369360.7	TSL:5	c.*188G>A		3_prime_UTR	Exon 41 of 41	ENSP00000358367.3	Q86VF7-3

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000207 AC: 92 AN: 443738 Hom.: 1 Cov.: 4 AF XY: 0.000218 AC XY: 51 AN XY: 233844

African (AFR) AF: 0.00 AC: 0 AN: 12360

American (AMR) AF: 0.0000575 AC: 1 AN: 17396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13532

East Asian (EAS) AF: 0.00 AC: 0 AN: 30740

South Asian (SAS) AF: 0.0000708 AC: 3 AN: 42390

European-Finnish (FIN) AF: 0.000570 AC: 18 AN: 31552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2058

European-Non Finnish (NFE) AF: 0.000243 AC: 65 AN: 267938

Other (OTH) AF: 0.000194 AC: 5 AN: 25772

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74478

African (AFR) AF: 0.0000722 AC: 3 AN: 41566

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.000566 AC: 6 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000476 Hom.: 0

Bravo AF: 0.000128

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	-0.86
CADD	Benign	4.1
DANN	Benign	0.60
PhyloP100		0.11
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: rs557625429; hg19: chr10-115348546;