Variant 1-6218354-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_207396.3(RNF207):c.1718A>G(p.Asn573Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,611,076 control chromosomes in the GnomAD database, including 109,978 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.44 ( 16854 hom., cov: 33)

Exomes 𝑓: 0.35 ( 93124 hom. )

Consequence

RNF207
NM_207396.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.309

Variant links:

Genes affected

RNF207 (HGNC:32947): (ring finger protein 207) Enables Hsp70 protein binding activity; chaperone binding activity; and transmembrane transporter binding activity. Involved in positive regulation of delayed rectifier potassium channel activity; positive regulation of gene expression; and positive regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization. Located in perinuclear region of cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RNF207 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=2.5483464E-6).

BP6

Variant 1-6218354-A-G is Benign according to our data. Variant chr1-6218354-A-G is described in ClinVar as [Benign]. Clinvar id is 1274153.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF207	NM_207396.3 linkuse as main transcript	c.1718A>G	p.Asn573Ser	missense_variant	17/18	ENST00000377939.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF207	ENST00000377939.5 linkuse as main transcript	c.1718A>G	p.Asn573Ser	missense_variant	17/18	5	NM_207396.3	P1	Q6ZRF8-1
RNF207	ENST00000483336.1 linkuse as main transcript	n.350A>G		non_coding_transcript_exon_variant	3/4	3
RNF207	ENST00000496676.5 linkuse as main transcript	n.1435A>G		non_coding_transcript_exon_variant	9/10	2

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66381

AN:

152000

Hom.:

16810

Cov.:

show subpopulations

Gnomad AFR

AF:

0.710

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.329

Gnomad ASJ

AF:

0.321

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.404

Gnomad FIN

AF:

0.298

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.421

GnomAD3 exomes

AF:

0.349

AC:

86771

AN:

248648

Hom.:

16917

AF XY:

0.352

AC XY:

47451

AN XY:

134974

show subpopulations

Gnomad AFR exome

AF:

0.716

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.253

Gnomad SAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.343

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.349

AC:

509530

AN:

1458958

Hom.:

93124

Cov.:

AF XY:

0.351

AC XY:

254635

AN XY:

725910

show subpopulations

Gnomad4 AFR exome

AF:

0.725

Gnomad4 AMR exome

AF:

0.242

Gnomad4 ASJ exome

AF:

0.328

Gnomad4 EAS exome

AF:

0.292

Gnomad4 SAS exome

AF:

0.415

Gnomad4 FIN exome

AF:

0.294

Gnomad4 NFE exome

AF:

0.342

Gnomad4 OTH exome

AF:

0.358

GnomAD4 genome

AF:

0.437

AC:

66474

AN:

152118

Hom.:

16854

Cov.:

AF XY:

0.434

AC XY:

32298

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.710

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.321

Gnomad4 EAS

AF:

0.264

Gnomad4 SAS

AF:

0.404

Gnomad4 FIN

AF:

0.298

Gnomad4 NFE

AF:

0.339

Gnomad4 OTH

AF:

0.422

Alfa

AF:

0.359

Hom.:

23465

Bravo

AF:

0.448

TwinsUK

AF:

0.347

AC:

1288

ALSPAC

AF:

0.346

AC:

1333

ESP6500AA

AF:

0.680

AC:

2908

ESP6500EA

AF:

0.336

AC:

2857

ExAC

AF:

0.361

AC:

43664

Asia WGS

AF:

0.404

AC:

1408

AN:

3478

EpiCase

AF:

0.354

EpiControl

AF:

0.349

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

GeneDx

Jul 13, 2018

This variant is associated with the following publications: (PMID: 28379579, 29874175) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.31

DANN

Benign

0.26

DEOGEN2

Benign

0.00063

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0000025

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.2

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

0.58

REVEL

Benign

0.023

Sift

Benign

1.0

Sift4G

Benign

0.72

Polyphen

0.0

Vest4

0.026

MPC

0.13

ClinPred

0.0011

GERP RS

-1.3

Varity_R

0.018

gMVP

0.053

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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