rs6827357

Variant names:

• chr4-1065414-A-C
• rs6827357
• NM_001366919.1:c.575-7021T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

RNF212 Gene-Disease associations (from GenCC):

• spermatogenic failure 62

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RNF212	NM_001366919.1	c.575-7021T>G		intron_variant	Intron 9 of 11		NP_001353848.1
RNF212	NM_001366918.1	c.575-7021T>G		intron_variant	Intron 9 of 10		NP_001353847.1
RNF212	XM_047450082.1	c.775-7021T>G		intron_variant	Intron 10 of 11		XP_047306038.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000698262.1	c.575-7021T>G		intron_variant	Intron 9 of 11			ENSP00000513634.1
RNF212	ENST00000503206.5	n.148-7021T>G		intron_variant	Intron 3 of 4	3
RNF212	ENST00000505693.5	n.502-7021T>G		intron_variant	Intron 3 of 5	5

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

African (AFR) AF: 0.889 AC: 36936 AN: 41548

American (AMR) AF: 0.680 AC: 10397 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2717 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3194 AN: 5172

South Asian (SAS) AF: 0.757 AC: 3651 AN: 4822

European-Finnish (FIN) AF: 0.805 AC: 8528 AN: 10598

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53341 AN: 68016

Other (OTH) AF: 0.781 AC: 1652 AN: 2114

Alfa AF: 0.803 Hom.: 9679

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
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs6827357; hg19: chr4-1059202;