5-111941787-G-T

Variant names:

• chr5-111941787-G-T
• rs6881837
• NM_001142475.2:c.135+33487C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001142475.2(NREP):​c.135+33487C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,842 control chromosomes in the GnomAD database, including 22,977 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 0.54 (22977 hom., cov: 32)
• Consequence: NREP NM_001142475.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.927
• Publications: 0 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NREP	NM_001142475.2		c.135+33487C>A		intron	N/A	NP_001135947.1	Q16612-2
	NREP	NM_001142474.2		c.105+33517C>A		intron	N/A	NP_001135946.1
	NREP-AS1	NR_046678.1		n.311+1653G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NREP	ENST00000395634.7	TSL:2	c.135+33487C>A		intron	N/A	ENSP00000378996.3	Q16612-2
	NREP	ENST00000450761.6	TSL:4	c.-59+55537C>A		intron	N/A	ENSP00000416617.2	Q16612-1
	NREP-AS1	ENST00000507222.5	TSL:3	n.311+1653G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81418 AN: 151726 Hom.: 22955 Cov.: 32

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.537 AC: 81483 AN: 151842 Hom.: 22977 Cov.: 32 AF XY: 0.544 AC XY: 40340 AN XY: 74162

African (AFR) AF: 0.689 AC: 28594 AN: 41474

American (AMR) AF: 0.574 AC: 8751 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 1434 AN: 3470

East Asian (EAS) AF: 0.568 AC: 2920 AN: 5142

South Asian (SAS) AF: 0.649 AC: 3122 AN: 4814

European-Finnish (FIN) AF: 0.502 AC: 5286 AN: 10536

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29811 AN: 67852

Other (OTH) AF: 0.511 AC: 1077 AN: 2106

Alfa AF: 0.424 Hom.: 1663

Bravo AF: 0.545

Asia WGS AF: 0.613 AC: 2131 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.56
DANN	Benign	0.33
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

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: rs6881837; hg19: chr5-111277484;