5-111941111-C-T

Position:

• chr5-111941111-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001142475.2(NREP):​c.135+34163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0172 in 151,938 control chromosomes in the GnomAD database, including 37 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 0.017 (37 hom., cov: 32)
• Consequence: NREP NM_001142475.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0172 (2616/151938) while in subpopulation AFR AF= 0.0402 (1668/41444). AF 95% confidence interval is 0.0386. There are 37 homozygotes in gnomad4. There are 1310 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NREP	NM_001142475.2	c.135+34163G>A		intron_variant			NP_001135947.1
NREP	NM_001142474.2	c.105+34193G>A		intron_variant			NP_001135946.1
NREP-AS1	NR_046678.1	n.311+977C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NREP	ENST00000395634.7	c.135+34163G>A		intron_variant		2		ENSP00000378996.3
NREP	ENST00000450761.6	c.-59+56213G>A		intron_variant		4		ENSP00000416617.2
NREP-AS1	ENST00000507222.5	n.311+977C>T		intron_variant		3
NREP-AS1	ENST00000508389.1	n.82+977C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2612 AN: 151820 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0107

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.00398

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00590

Gnomad OTH AF: 0.0105

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

GnomAD4 genome AF: 0.0172 AC: 2616 AN: 151938 Hom.: 37 Cov.: 32 AF XY: 0.0176 AC XY: 1310 AN XY: 74272

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0105

Gnomad4 SAS AF: 0.0365

Gnomad4 FIN AF: 0.00398

Gnomad4 NFE AF: 0.00590

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00966 Hom.: 14

Bravo AF: 0.0186

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs10515437; hg19: chr5-111276808;