dbSNP rs775070398: NREP:p.Leu7Arg (chr5-111735491-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_004772.4(NREP):c.20T>G(p.Leu7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NREP
NM_004772.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.997

Variant links:

Genes affected

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]

NREP links:

STARD4-AS1 (HGNC:44117): (STARD4 antisense RNA 1)

STARD4-AS1 links:

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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=0.17876121).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NREP	NM_004772.4 link	c.20T>G	p.Leu7Arg	missense_variant	Exon 3 of 4	ENST00000257435.12	NP_004763.1	Q16612-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NREP	ENST00000257435.12 link	c.20T>G	p.Leu7Arg	missense_variant	Exon 3 of 4	1	NM_004772.4	ENSP00000257435.7		Q16612-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

250970

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135654

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459992

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726388

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.45

.;T;T;T;T;.;.;.;T;T;T;T;T;T;.;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.057

LIST_S2

Benign

0.64

T;.;.;T;.;T;.;T;.;.;.;.;.;.;T;T

M_CAP

Benign

0.038

MetaRNN

Benign

0.18

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-5.8

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

REVEL

Benign

0.23

Sift

Benign

0.043

D;T;T;T;T;D;D;D;T;T;T;T;T;T;T;D

Sift4G

Pathogenic

0.0

D;T;T;T;T;D;D;D;T;T;T;T;T;T;.;.

Polyphen

0.98, 1.0

.;D;D;D;D;.;.;.;D;D;D;D;D;D;D;.

Vest4

0.72

MutPred

0.37

Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);.;Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);Gain of disorder (P = 0.0157);

MVP

0.85

MPC

0.92

ClinPred

0.78

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.21

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