Variant chr10-113590838-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_198060.4(NRAP):c.4696C>T(p.Arg1566Cys) variant causes a missense change. The variant allele was found at a frequency of 0.347 in 1,613,718 control chromosomes in the GnomAD database, including 98,739 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 10708 hom., cov: 32)

Exomes 𝑓: 0.35 ( 88031 hom. )

Consequence

NRAP
NM_198060.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.61

Variant links:

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]

NRAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027224123).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRAP	NM_198060.4 linkuse as main transcript	c.4696C>T	p.Arg1566Cys	missense_variant	40/42	ENST00000359988.4	NP_932326.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRAP	ENST00000359988.4 linkuse as main transcript	c.4696C>T	p.Arg1566Cys	missense_variant	40/42	1	NM_198060.4	ENSP00000353078	A1	Q86VF7-1
NRAP	ENST00000369358.8 linkuse as main transcript	c.4696C>T	p.Arg1566Cys	missense_variant	40/42	1		ENSP00000358365	P5
NRAP	ENST00000360478.7 linkuse as main transcript	c.4591C>T	p.Arg1531Cys	missense_variant	39/41	1		ENSP00000353666		Q86VF7-4
NRAP	ENST00000369360.7 linkuse as main transcript	c.4615C>T	p.Arg1539Cys	missense_variant	39/41	5		ENSP00000358367		Q86VF7-3

Frequencies

GnomAD3 genomes

AF:

0.370

AC:

56256

AN:

151934

Hom.:

10695

Cov.:

show subpopulations

Gnomad AFR

AF:

0.416

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.462

Gnomad ASJ

AF:

0.340

Gnomad EAS

AF:

0.319

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.365

GnomAD3 exomes

AF:

0.359

AC:

89922

AN:

250634

Hom.:

16693

AF XY:

0.352

AC XY:

47639

AN XY:

135506

show subpopulations

Gnomad AFR exome

AF:

0.412

Gnomad AMR exome

AF:

0.497

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.306

Gnomad SAS exome

AF:

0.322

Gnomad FIN exome

AF:

0.299

Gnomad NFE exome

AF:

0.340

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.345

AC:

504358

AN:

1461666

Hom.:

88031

Cov.:

AF XY:

0.344

AC XY:

249784

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.414

Gnomad4 AMR exome

AF:

0.488

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.314

Gnomad4 SAS exome

AF:

0.320

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.345

GnomAD4 genome

AF:

0.370

AC:

56310

AN:

152052

Hom.:

10708

Cov.:

AF XY:

0.368

AC XY:

27341

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.416

Gnomad4 AMR

AF:

0.462

Gnomad4 ASJ

AF:

0.340

Gnomad4 EAS

AF:

0.319

Gnomad4 SAS

AF:

0.320

Gnomad4 FIN

AF:

0.294

Gnomad4 NFE

AF:

0.343

Gnomad4 OTH

AF:

0.363

Alfa

AF:

0.348

Hom.:

23281

Bravo

AF:

0.383

TwinsUK

AF:

0.337

AC:

1249

ALSPAC

AF:

0.349

AC:

1344

ESP6500AA

AF:

0.408

AC:

1797

ESP6500EA

AF:

0.348

AC:

2996

ExAC

AF:

0.353

AC:

42879

Asia WGS

AF:

0.320

AC:

1112

AN:

3478

EpiCase

AF:

0.336

EpiControl

AF:

0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;.;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.023

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D;D;D

MetaRNN

Benign

0.0027

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.7

.;.;.;M

MutationTaster

Benign

0.00065

P;P;P;P;P

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-6.5

D;D;.;D

REVEL

Benign

0.11

Sift

Benign

0.039

D;D;.;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.024, 0.014

.;B;.;B

Vest4

0.30

MPC

0.097

ClinPred

0.077

GERP RS

3.8

Varity_R

0.23

gMVP

0.54

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over