rs2286735
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_198060.4(NRAP):c.2021C>T(p.Ala674Val) variant causes a missense change. The variant allele was found at a frequency of 0.308 in 1,607,510 control chromosomes in the GnomAD database, including 78,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.28 ( 6360 hom., cov: 32)
Exomes 𝑓: 0.31 ( 71852 hom. )
Consequence
NRAP
NM_198060.4 missense
NM_198060.4 missense
Scores
5
11
Clinical Significance
Conservation
PhyloP100: 6.92
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0049262047).
BP6
?
Variant 10-113629607-G-A is Benign according to our data. Variant chr10-113629607-G-A is described in ClinVar as [Benign]. Clinvar id is 1269749.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.35 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NRAP | NM_198060.4 | c.2021C>T | p.Ala674Val | missense_variant | 19/42 | ENST00000359988.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NRAP | ENST00000359988.4 | c.2021C>T | p.Ala674Val | missense_variant | 19/42 | 1 | NM_198060.4 | A1 | |
NRAP | ENST00000369358.8 | c.2021C>T | p.Ala674Val | missense_variant | 19/42 | 1 | P5 | ||
NRAP | ENST00000360478.7 | c.1916C>T | p.Ala639Val | missense_variant | 18/41 | 1 | |||
NRAP | ENST00000369360.7 | c.1940C>T | p.Ala647Val | missense_variant | 18/41 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.285 AC: 43185AN: 151752Hom.: 6338 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
43185
AN:
151752
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.317 AC: 79598AN: 251088Hom.: 13244 AF XY: 0.316 AC XY: 42841AN XY: 135706
GnomAD3 exomes
AF:
AC:
79598
AN:
251088
Hom.:
AF XY:
AC XY:
42841
AN XY:
135706
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.311 AC: 452188AN: 1455638Hom.: 71852 Cov.: 32 AF XY: 0.310 AC XY: 224783AN XY: 724486
GnomAD4 exome
AF:
AC:
452188
AN:
1455638
Hom.:
Cov.:
32
AF XY:
AC XY:
224783
AN XY:
724486
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.285 AC: 43251AN: 151872Hom.: 6360 Cov.: 32 AF XY: 0.288 AC XY: 21379AN XY: 74200
GnomAD4 genome
?
AF:
AC:
43251
AN:
151872
Hom.:
Cov.:
32
AF XY:
AC XY:
21379
AN XY:
74200
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
1201
ALSPAC
AF:
AC:
1243
ESP6500AA
AF:
AC:
940
ESP6500EA
AF:
AC:
2620
ExAC
?
AF:
AC:
37694
Asia WGS
AF:
AC:
966
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P;P;P
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;.;D
REVEL
Benign
Sift
Benign
T;T;.;T
Sift4G
Benign
T;T;T;T
Polyphen
0.0020, 0.0010
.;B;.;B
Vest4
MPC
0.077
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at