rs756211201

Variant names:

• chr5-111975374-C-A
• rs756211201
• NM_001142475.2:c.35G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-111975374-C-A
• chr5-111975374-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001142475.2(NREP):​c.35G>T​(p.Arg12Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R12Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NREP NM_001142475.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052175134).

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.35G>T	p.Arg12Leu	missense	Exon 2 of 4	NP_001135947.1	Q16612-2
	NREP	NM_001142474.2		c.35G>T	p.Arg12Leu	missense	Exon 2 of 4	NP_001135946.1
	NREP-AS1	NR_046678.1		n.443+868C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NREP	ENST00000395634.7	TSL:2	c.35G>T	p.Arg12Leu	missense	Exon 2 of 4	ENSP00000378996.3	Q16612-2
	NREP	ENST00000450761.6	TSL:4	c.-59+21950G>T		intron	N/A	ENSP00000416617.2	Q16612-1
	NREP-AS1	ENST00000503242.1	TSL:3	n.241+868C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398956 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690030

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.00 AC: 0 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25174

East Asian (EAS) AF: 0.00 AC: 0 AN: 35732

South Asian (SAS) AF: 0.00 AC: 0 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078584

Other (OTH) AF: 0.00 AC: 0 AN: 57986

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.64
DANN	Benign	0.93
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.45
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.027
Sift	Pathogenic	0.0	D
Vest4		0.14
MutPred		0.24		Loss of disorder (P = 0.0081)
MVP		0.19
MPC		0.26
ClinPred		0.32	T
GERP RS		-2.1
gMVP		0.0076
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: rs756211201; hg19: chr5-111311071;