rs10515438

chr5-111966867-G-Cchr5-111966867-G-T

Variant summary

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

The NR_046678.1(NREP-AS1):n.312-7508G>C 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 0.0211 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-AS1 NR_046678.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NREP-AS1	NR_046678.1	n.312-7508G>C		intron_variant, non_coding_transcript_variant
NREP	NM_001142474.2	c.105+8437C>G		intron_variant
NREP	NM_001142475.2	c.135+8407C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NREP-AS1	ENST00000507222.5	n.312-7508G>C		intron_variant, non_coding_transcript_variant		3
NREP	ENST00000395634.7	c.135+8407C>G		intron_variant		2
NREP	ENST00000450761.6	c.-59+30457C>G		intron_variant		4		P1

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

Gnomad4 AFR AF: 0.00542

Gnomad4 AMR AF: 0.0125

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.0305

Gnomad4 SAS AF: 0.0293

Gnomad4 FIN AF: 0.0450

Gnomad4 NFE AF: 0.0286

Gnomad4 OTH AF: 0.0147

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

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: rs10515438; hg19: chr5-111302564;