Variant 1-40240054-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012421.4(RLF):c.5352A>T(p.Glu1784Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,613,606 control chromosomes in the GnomAD database, including 32,781 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.20 ( 3274 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29507 hom. )

Consequence

RLF
NM_012421.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.30

Variant links:

Genes affected

RLF (HGNC:10025): (RLF zinc finger) Predicted to enable DNA binding activity and DNA-binding transcription activator activity, RNA polymerase II-specific. Predicted to be involved in positive regulation of transcription by RNA polymerase II. Predicted to act upstream of or within histone H3-K4 monomethylation and regulation of DNA methylation. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RLF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015485883).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RLF	NM_012421.4 linkuse as main transcript	c.5352A>T	p.Glu1784Asp	missense_variant	8/8	ENST00000372771.5
RLF	XM_047427055.1 linkuse as main transcript	c.4704A>T	p.Glu1568Asp	missense_variant	6/6
RLF	XM_047427057.1 linkuse as main transcript	c.4185A>T	p.Glu1395Asp	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLF	ENST00000372771.5 linkuse as main transcript	c.5352A>T	p.Glu1784Asp	missense_variant	8/8	1	NM_012421.4	P1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30771

AN:

152066

Hom.:

3271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.0569

Gnomad SAS

AF:

0.0681

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.201

GnomAD3 exomes

AF:

0.176

AC:

44174

AN:

250630

Hom.:

4354

AF XY:

0.171

AC XY:

23209

AN XY:

135534

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.164

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.0498

Gnomad SAS exome

AF:

0.0746

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.208

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.196

AC:

286255

AN:

1461422

Hom.:

29507

Cov.:

AF XY:

0.191

AC XY:

139085

AN XY:

727026

show subpopulations

Gnomad4 AFR exome

AF:

0.237

Gnomad4 AMR exome

AF:

0.165

Gnomad4 ASJ exome

AF:

0.146

Gnomad4 EAS exome

AF:

0.0742

Gnomad4 SAS exome

AF:

0.0761

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.202

AC:

30775

AN:

152184

Hom.:

3274

Cov.:

AF XY:

0.200

AC XY:

14903

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.239

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.0571

Gnomad4 SAS

AF:

0.0671

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.198

Alfa

AF:

0.198

Hom.:

2325

Bravo

AF:

0.197

TwinsUK

AF:

0.211

AC:

781

ALSPAC

AF:

0.214

AC:

826

ESP6500AA

AF:

0.227

AC:

1001

ESP6500EA

AF:

0.200

AC:

1718

ExAC

AF:

0.176

AC:

21324

Asia WGS

AF:

0.0730

AC:

254

AN:

3478

EpiCase

AF:

0.202

EpiControl

AF:

0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.88

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.010

DANN

Benign

0.28

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.43

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.050

REVEL

Benign

0.058

Sift

Benign

0.62

Sift4G

Benign

0.85

Polyphen

0.0

Vest4

0.026

MutPred

0.15

Gain of helix (P = 0.0325);

MPC

0.36

ClinPred

0.0053

GERP RS

-12

Varity_R

0.034

gMVP

0.049

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over