chr5-111735491-A-C

Variant names:

• chr5-111735491-A-C
• rs775070398
• NM_004772.4:c.20T>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.20T>G​(p.Leu7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. L7P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NREP NM_004772.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.997
• 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=0.17876121).

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.20T>G	p.Leu7Arg	missense	Exon 3 of 4	NP_004763.1	Q16612-1
	NREP	NM_001142475.2		c.152T>G	p.Leu51Arg	missense	Exon 3 of 4	NP_001135947.1	Q16612-2
	NREP	NM_001142474.2		c.122T>G	p.Leu41Arg	missense	Exon 3 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.20T>G	p.Leu7Arg	missense	Exon 3 of 4	ENSP00000257435.7	Q16612-1
	NREP	ENST00000379671.7	TSL:1	c.20T>G	p.Leu7Arg	missense	Exon 4 of 5	ENSP00000368993.3	Q16612-1
	NREP	ENST00000447165.6	TSL:1	c.20T>G	p.Leu7Arg	missense	Exon 2 of 3	ENSP00000408839.2	Q16612-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250970 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459992 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 726388

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53164

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

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110650

Other (OTH) AF: 0.00 AC: 0 AN: 60310

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.45	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.0
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.23
Sift	Benign	0.043	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.72
MutPred		0.37		Gain of disorder (P = 0.0157)
MVP		0.85
MPC		0.92
ClinPred		0.78	D
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.13
gMVP		0.21
Mutation Taster		=96/4	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: rs775070398; hg19: chr5-111071188;