rs2419854

Variant names:

• chr10-113632352-A-G
• rs2419854
• NM_198060.4:c.1633-388T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198060.4(NRAP):​c.1633-388T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 152,234 control chromosomes in the GnomAD database, including 6,464 homozygotes. 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: 𝑓 0.29 (6464 hom., cov: 33)
• Consequence: NRAP NM_198060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRAP	NM_198060.4	c.1633-388T>C		intron_variant	Intron 16 of 41	ENST00000359988.4	NP_932326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRAP	ENST00000359988.4	c.1633-388T>C		intron_variant	Intron 16 of 41	1	NM_198060.4	ENSP00000353078.3
NRAP	ENST00000369358.8	c.1633-388T>C		intron_variant	Intron 16 of 41	1		ENSP00000358365.4
NRAP	ENST00000360478.7	c.1528-388T>C		intron_variant	Intron 15 of 40	1		ENSP00000353666.3
NRAP	ENST00000369360.7	c.1528-388T>C		intron_variant	Intron 15 of 40	5		ENSP00000358367.3

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43425 AN: 152116 Hom.: 6443 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.269

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.286 AC: 43490 AN: 152234 Hom.: 6464 Cov.: 33 AF XY: 0.289 AC XY: 21531 AN XY: 74428

African (AFR) AF: 0.217 AC: 8995 AN: 41546

American (AMR) AF: 0.359 AC: 5496 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3470

East Asian (EAS) AF: 0.289 AC: 1497 AN: 5182

South Asian (SAS) AF: 0.300 AC: 1446 AN: 4828

European-Finnish (FIN) AF: 0.311 AC: 3296 AN: 10598

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.308 AC: 20911 AN: 67990

Other (OTH) AF: 0.265 AC: 560 AN: 2116

Alfa AF: 0.301 Hom.: 1277

Bravo AF: 0.290

Asia WGS AF: 0.280 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.44
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs2419854; hg19: chr10-115392111;