Variant 1-40202583-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012421.4(RLF):c.779C>G(p.Ser260Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00287 in 1,546,532 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 51 hom. )

Consequence

RLF
NM_012421.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.99

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045910478).

BP6

Variant 1-40202583-C-G is Benign according to our data. Variant chr1-40202583-C-G is described in ClinVar as [Benign]. Clinvar id is 771304.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00347 (529/152246) while in subpopulation EAS AF= 0.0301 (156/5184). AF 95% confidence interval is 0.0262. There are 11 homozygotes in gnomad4. There are 295 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 529 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RLF	NM_012421.4 linkuse as main transcript	c.779C>G	p.Ser260Cys	missense_variant	5/8	ENST00000372771.5
RLF	XM_047427055.1 linkuse as main transcript	c.131C>G	p.Ser44Cys	missense_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLF	ENST00000372771.5 linkuse as main transcript	c.779C>G	p.Ser260Cys	missense_variant	5/8	1	NM_012421.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00348

AC:

529

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0175

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.0300

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.000755

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000926

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00646

AC:

1249

AN:

193200

Hom.:

AF XY:

0.00526

AC XY:

561

AN XY:

106628

show subpopulations

Gnomad AFR exome

AF:

0.000614

Gnomad AMR exome

AF:

0.0453

Gnomad ASJ exome

AF:

0.000125

Gnomad EAS exome

AF:

0.0270

Gnomad SAS exome

AF:

0.00124

Gnomad FIN exome

AF:

0.000630

Gnomad NFE exome

AF:

0.000889

Gnomad OTH exome

AF:

0.00322

GnomAD4 exome

AF:

0.00280

AC:

3907

AN:

1394286

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

1837

AN XY:

692746

show subpopulations

Gnomad4 AFR exome

AF:

0.000243

Gnomad4 AMR exome

AF:

0.0368

Gnomad4 ASJ exome

AF:

0.000290

Gnomad4 EAS exome

AF:

0.0404

Gnomad4 SAS exome

AF:

0.00127

Gnomad4 FIN exome

AF:

0.00111

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.00228

GnomAD4 genome

AF:

0.00347

AC:

529

AN:

152246

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0175

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.0301

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000755

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00229

Hom.:

Bravo

AF:

0.00563

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00773

AC:

939

Asia WGS

AF:

0.0140

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.022

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.9

REVEL

Benign

0.17

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.022

Polyphen

1.0

Vest4

0.72

MVP

0.36

MPC

0.76

ClinPred

0.013

GERP RS

5.0

Varity_R

0.20

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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