rs6827357

Positions:

• chr4-1065414-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001366919.1(RNF212):​c.575-7021T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.796 in 152,238 control chromosomes in the GnomAD database, including 48,736 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (48736 hom., cov: 34)
• Consequence: RNF212 NM_001366919.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

Genes affected

RNF212 (HGNC:27729): (ring finger protein 212) This gene encodes a RING finger protein that may function as a ubiquitin ligase. The encoded protein may be involved in meiotic recombination. This gene is located within a linkage disequilibrium block and polymorphisms in this gene may influence recombination rates. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF212	NM_001366918.1	c.575-7021T>G		intron_variant			NP_001353847.1
RNF212	NM_001366919.1	c.575-7021T>G		intron_variant			NP_001353848.1
RNF212	XM_011513446.2	c.311-7021T>G		intron_variant			XP_011511748.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000698262.1	c.575-7021T>G		intron_variant				ENSP00000513634	P2
RNF212	ENST00000506730.5	c.*354-7021T>G		intron_variant, NMD_transcript_variant		3		ENSP00000425843
RNF212	ENST00000503206.5	n.148-7021T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.796 AC: 121152 AN: 152120 Hom.: 48718 Cov.: 34

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.783

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.796 AC: 121217 AN: 152238 Hom.: 48736 Cov.: 34 AF XY: 0.793 AC XY: 59002 AN XY: 74428

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.680

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.618

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.784

Gnomad4 OTH AF: 0.781

Alfa AF: 0.795 Hom.: 7841

Bravo AF: 0.789

Asia WGS AF: 0.662 AC: 2303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6827357; hg19: chr4-1059202;