dbSNP rs10515438: NREP:c.135+8407C>G (chr5-111966867-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001142475.2(NREP):c.135+8407C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 152,214 control chromosomes in the GnomAD database, including 50 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 0.021 ( 50 hom., cov: 32)

Consequence

NREP
NM_001142475.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.391

Publications

1 publications found

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:

NREP-AS1 (HGNC:40780): (NREP antisense RNA 1)

NREP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0211 (3209/152214) while in subpopulation EAS AF = 0.0305 (158/5184). AF 95% confidence interval is 0.0275. There are 50 homozygotes in GnomAd4. There are 1649 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142475.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
NREP	NM_001142475.2	c.135+8407C>G	intron	N/A	NP_001135947.1	Q16612-2
NREP	NM_001142474.2	c.105+8437C>G	intron	N/A	NP_001135946.1
NREP-AS1	NR_046678.1	n.312-7508G>C	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NREP	ENST00000395634.7	TSL:2	c.135+8407C>G	intron	N/A	ENSP00000378996.3	Q16612-2
NREP	ENST00000450761.6	TSL:4	c.-59+30457C>G	intron	N/A	ENSP00000416617.2	Q16612-1
NREP-AS1	ENST00000507222.5	TSL:3	n.312-7508G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3206

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00543

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0306

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.0450

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0286

Gnomad OTH

AF:

0.0153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0211

AC:

3209

AN:

152214

Hom.:

Cov.:

AF XY:

0.0222

AC XY:

1649

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00542

AC:

225

AN:

41522

American (AMR)

AF:

0.0125

AC:

191

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3468

East Asian (EAS)

AF:

0.0305

AC:

158

AN:

5184

South Asian (SAS)

AF:

0.0293

AC:

141

AN:

4812

European-Finnish (FIN)

AF:

0.0450

AC:

477

AN:

10602

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0286

AC:

1943

AN:

68014

Other (OTH)

AF:

0.0147

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

167

334

501

668

835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00949

Hom.:

Bravo

AF:

0.0178

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.38

(source)

DANN

Benign

0.74

PhyloP100

-0.39

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over