Variant 5-111975374-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NR_046678.1(NREP-AS1):n.443+868C>T 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 0.0000387 in 1,551,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

NREP-AS1
NR_046678.1 intron, non_coding_transcript

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.448

Variant links:

Genes affected

NREP-AS1 (HGNC:40780): (NREP antisense RNA 1)

NREP-AS1 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036646515).

BP6

Variant 5-111975374-C-T is Benign according to our data. Variant chr5-111975374-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2401003.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
NREP-AS1	NR_046678.1 linkuse as main transcript	n.443+868C>T		intron_variant, non_coding_transcript_variant
NREP	NM_001142475.2 linkuse as main transcript	c.35G>A	p.Arg12Gln	missense_variant	2/4
NREP	NM_001142474.2 linkuse as main transcript	c.35G>A	p.Arg12Gln	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
NREP-AS1	ENST00000507222.5 linkuse as main transcript	n.443+868C>T		intron_variant, non_coding_transcript_variant		3
NREP	ENST00000395634.7 linkuse as main transcript	c.35G>A	p.Arg12Gln	missense_variant	2/4	2		Q16612-2
NREP	ENST00000450761.6 linkuse as main transcript	c.-59+21950G>A		intron_variant		4	P1	Q16612-1
NREP-AS1	ENST00000503242.1 linkuse as main transcript	n.241+868C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000130

AC:

AN:

153976

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81702

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000168

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000264

AC:

AN:

1398956

Hom.:

Cov.:

AF XY:

0.0000348

AC XY:

AN XY:

690030

show subpopulations

Gnomad4 AFR exome

AF:

0.000380

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000195

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.000151

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.000531

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000659

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.0000430

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.1

DANN

Benign

0.92

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0086

LIST_S2

Benign

0.34

M_CAP

Benign

0.0076

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.69

REVEL

Benign

0.085

Sift

Pathogenic

0.0

Vest4

0.040

MVP

0.25

MPC

0.23

ClinPred

0.066

GERP RS

-2.1

gMVP

0.0033

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over