5-111966867-G-C

Variant names:

• chr5-111966867-G-C
• rs10515438
• NM_001142475.2:c.135+8407C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 1 publications found

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

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NREP	NM_001142475.2	c.135+8407C>G		intron_variant	Intron 2 of 3		NP_001135947.1
NREP	NM_001142474.2	c.105+8437C>G		intron_variant	Intron 2 of 3		NP_001135946.1
NREP-AS1	NR_046678.1	n.312-7508G>C		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NREP	ENST00000395634.7	c.135+8407C>G		intron_variant	Intron 2 of 3	2		ENSP00000378996.3
NREP	ENST00000450761.6	c.-59+30457C>G		intron_variant	Intron 1 of 3	4		ENSP00000416617.2
NREP-AS1	ENST00000507222.5	n.312-7508G>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3206 AN: 152096 Hom.: 50 Cov.: 32

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.: 50 Cov.: 32 AF XY: 0.0222 AC XY: 1649 AN XY: 74438

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: 35 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: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0286 AC: 1943 AN: 68014

Other (OTH) AF: 0.0147 AC: 31 AN: 2110

Alfa AF: 0.00949 Hom.: 4

Bravo AF: 0.0178

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.74
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs10515438; hg19: chr5-111302564;