rs372931840

Variant names:

• chr5-111730944-T-C
• rs372931840
• NM_004772.4:c.184A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004772.4(NREP):​c.184A>G​(p.Ile62Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NREP NM_004772.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18
• 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]

STARD4-AS1 (HGNC:44117): (STARD4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14202935).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004772.4. 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_004772.4	MANE Select	c.184A>G	p.Ile62Val	missense	Exon 4 of 4	NP_004763.1	Q16612-1
	NREP	NM_001142475.2		c.316A>G	p.Ile106Val	missense	Exon 4 of 4	NP_001135947.1	Q16612-2
	NREP	NM_001142474.2		c.286A>G	p.Ile96Val	missense	Exon 4 of 4	NP_001135946.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NREP	ENST00000257435.12	TSL:1 MANE Select	c.184A>G	p.Ile62Val	missense	Exon 4 of 4	ENSP00000257435.7	Q16612-1
	NREP	ENST00000379671.7	TSL:1	c.184A>G	p.Ile62Val	missense	Exon 5 of 5	ENSP00000368993.3	Q16612-1
	NREP	ENST00000447165.6	TSL:1	c.184A>G	p.Ile62Val	missense	Exon 3 of 3	ENSP00000408839.2	Q16612-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461628 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727126

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111818

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.35
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.038
Sift	Benign	0.21	T
Sift4G	Benign	0.32	T
Polyphen		0.013	B
Vest4		0.085
MVP		0.55
MPC		0.27
ClinPred		0.51	D
GERP RS		2.6
Varity_R		0.024
gMVP		0.045
Mutation Taster		=95/5	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: rs372931840; hg19: chr5-111066641;