rs1113394

chr10-113621583-C-Achr10-113621583-C-Gchr10-113621583-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
NRAP	NM_198060.4	c.2769+286G>T		intron_variant		ENST00000359988.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRAP	ENST00000359988.4	c.2769+286G>T		intron_variant		1	NM_198060.4	A1
NRAP	ENST00000360478.7	c.2664+286G>T		intron_variant		1
NRAP	ENST00000369358.8	c.2769+286G>T		intron_variant		1		P5
NRAP	ENST00000369360.7	c.2688+286G>T		intron_variant		5

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

Gnomad4 AFR AF: 0.0354

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.176

Gnomad4 OTH AF: 0.147

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1113394; hg19: chr10-115381342;