chr5-111975314-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NR_046678.1(NREP-AS1):​n.443+808T>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000035 in 1,399,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

NREP-AS1
NR_046678.1 intron, non_coding_transcript

Scores

1
1
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.581
Variant links:
Genes affected
NREP-AS1 (HGNC:40780): (NREP antisense RNA 1)
NREP (HGNC:16834): (neuronal regeneration related protein) Predicted to be involved in axon regeneration; regulation of neuron differentiation; and regulation of transforming growth factor beta receptor signaling pathway. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.073062986).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NREP-AS1NR_046678.1 linkuse as main transcriptn.443+808T>A intron_variant, non_coding_transcript_variant
NREPNM_001142475.2 linkuse as main transcriptc.95A>T p.Lys32Ile missense_variant 2/4
NREPNM_001142474.2 linkuse as main transcriptc.95A>T p.Lys32Ile missense_variant 2/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NREP-AS1ENST00000507222.5 linkuse as main transcriptn.443+808T>A intron_variant, non_coding_transcript_variant 3
NREPENST00000395634.7 linkuse as main transcriptc.95A>T p.Lys32Ile missense_variant 2/42 Q16612-2
NREPENST00000450761.6 linkuse as main transcriptc.-59+22010A>T intron_variant 4 P1Q16612-1
NREP-AS1ENST00000503242.1 linkuse as main transcriptn.241+808T>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000260
AC:
4
AN:
154020
Hom.:
0
AF XY:
0.0000367
AC XY:
3
AN XY:
81720
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000671
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000350
AC:
49
AN:
1399324
Hom.:
0
Cov.:
30
AF XY:
0.0000449
AC XY:
31
AN XY:
690170
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000445
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 27, 2023The c.95A>T (p.K32I) alteration is located in exon 2 (coding exon 2) of the NREP gene. This alteration results from a A to T substitution at nucleotide position 95, causing the lysine (K) at amino acid position 32 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.71
DANN
Uncertain
0.98
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.015
N
LIST_S2
Benign
0.26
T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.073
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.94
N
REVEL
Benign
0.028
Sift
Pathogenic
0.0
D
Vest4
0.16
MVP
0.20
MPC
0.59
ClinPred
0.048
T
GERP RS
-1.7
gMVP
0.027

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.

Other links and lift over

dbSNP: rs1041874413; hg19: chr5-111311011; API