1-6219310-G-C

Variant names:

• chr1-6219310-G-C
• rs846111
• NM_207396.3:c.1808G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207396.3(RNF207):​c.1808G>C​(p.Gly603Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,612,148 control chromosomes in the GnomAD database, including 55,343 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3819 hom., cov: 31)
  • Exomes 𝑓: 0.26 (51524 hom.)
• Consequence: RNF207 NM_207396.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.117
• Publications: 77 publications found

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 Gene-Disease associations (from GenCC):

• long QT syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044692755).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207396.3. 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
	RNF207	NM_207396.3	MANE Select	c.1808G>C	p.Gly603Ala	missense	Exon 18 of 18	NP_997279.2	Q6ZRF8-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF207	ENST00000377939.5	TSL:5 MANE Select	c.1808G>C	p.Gly603Ala	missense	Exon 18 of 18	ENSP00000367173.4	Q6ZRF8-1
	RNF207	ENST00000951272.1		c.2069G>C	p.Gly690Ala	missense	Exon 20 of 20	ENSP00000621331.1
	RNF207	ENST00000882099.1		c.1892G>C	p.Gly631Ala	missense	Exon 18 of 18	ENSP00000552158.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30221 AN: 151884 Hom.: 3816 Cov.: 31

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.207

GnomAD2 exomes AF: 0.235 AC: 58518 AN: 248810 AF XY: 0.245

Gnomad AFR exome AF: 0.0480

Gnomad AMR exome AF: 0.147

Gnomad ASJ exome AF: 0.274

Gnomad EAS exome AF: 0.174

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.273

Gnomad OTH exome AF: 0.242

GnomAD4 exome AF: 0.261 AC: 380898 AN: 1460146 Hom.: 51524 Cov.: 32 AF XY: 0.263 AC XY: 191167 AN XY: 726416

African (AFR) AF: 0.0453 AC: 1516 AN: 33468

American (AMR) AF: 0.153 AC: 6842 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7107 AN: 26108

East Asian (EAS) AF: 0.212 AC: 8413 AN: 39672

South Asian (SAS) AF: 0.293 AC: 25230 AN: 86050

European-Finnish (FIN) AF: 0.255 AC: 13576 AN: 53274

Middle Eastern (MID) AF: 0.250 AC: 1424 AN: 5696

European-Non Finnish (NFE) AF: 0.272 AC: 302293 AN: 1110896

Other (OTH) AF: 0.240 AC: 14497 AN: 60308

GnomAD4 genome AF: 0.199 AC: 30217 AN: 152002 Hom.: 3819 Cov.: 31 AF XY: 0.201 AC XY: 14967 AN XY: 74282

African (AFR) AF: 0.0517 AC: 2146 AN: 41494

American (AMR) AF: 0.186 AC: 2835 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.180 AC: 926 AN: 5152

South Asian (SAS) AF: 0.287 AC: 1378 AN: 4796

European-Finnish (FIN) AF: 0.262 AC: 2762 AN: 10558

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.271 AC: 18446 AN: 67952

Other (OTH) AF: 0.208 AC: 439 AN: 2110

Alfa AF: 0.260 Hom.: 4121

Bravo AF: 0.185

TwinsUK AF: 0.288 AC: 1069

ALSPAC AF: 0.279 AC: 1076

ESP6500AA AF: 0.0586 AC: 219

ESP6500EA AF: 0.264 AC: 2163

ExAC AF: 0.235 AC: 28351

Asia WGS AF: 0.232 AC: 808 AN: 3478

EpiCase AF: 0.276

EpiControl AF: 0.271

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.42
DANN	Benign	0.45
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.42	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.12
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.76	N
REVEL	Benign	0.035
Sift	Benign	0.24	T
Sift4G	Benign	0.55	T
Polyphen		0.0030	B
Vest4		0.029
MPC		0.18
ClinPred		0.00050	T
GERP RS		1.0
Varity_R		0.042
gMVP		0.065
Mutation Taster		=100/0	polymorphism (auto)

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: rs846111; hg19: chr1-6279370; COSMIC: COSV59473171; COSMIC: COSV59473171;