NM_198060.4:c.2769+286G>T

Variant names:

• chr10-113621583-C-A
• rs1113394
• NM_198060.4:c.2769+286G>T

Variant summary

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

The NM_198060.4(NRAP):​c.2769+286G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,184 control chromosomes in the GnomAD database, including 2,133 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 0.14 (2133 hom., cov: 32)
• Consequence: NRAP NM_198060.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRAP	NM_198060.4	c.2769+286G>T		intron_variant	Intron 24 of 41	ENST00000359988.4	NP_932326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRAP	ENST00000359988.4	c.2769+286G>T		intron_variant	Intron 24 of 41	1	NM_198060.4	ENSP00000353078.3
NRAP	ENST00000369358.8	c.2769+286G>T		intron_variant	Intron 24 of 41	1		ENSP00000358365.4
NRAP	ENST00000360478.7	c.2664+286G>T		intron_variant	Intron 23 of 40	1		ENSP00000353666.3
NRAP	ENST00000369360.7	c.2688+286G>T		intron_variant	Intron 23 of 40	5		ENSP00000358367.3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21893 AN: 152066 Hom.: 2130 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.144 AC: 21904 AN: 152184 Hom.: 2133 Cov.: 32 AF XY: 0.148 AC XY: 10980 AN XY: 74400

African (AFR) AF: 0.0354 AC: 1469 AN: 41546

American (AMR) AF: 0.287 AC: 4382 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3472

East Asian (EAS) AF: 0.154 AC: 797 AN: 5176

South Asian (SAS) AF: 0.122 AC: 584 AN: 4806

European-Finnish (FIN) AF: 0.166 AC: 1754 AN: 10584

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 12001 AN: 68008

Other (OTH) AF: 0.147 AC: 311 AN: 2110

Alfa AF: 0.0457 Hom.: 45

Bravo AF: 0.152

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.045
DANN	Benign	0.64
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1113394; hg19: chr10-115381342;