4-1058378-A-C

Variant names:

• chr4-1058378-A-C
• rs2248083
• NM_001366919.1:c.590T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001366919.1(RNF212):​c.590T>G​(p.Leu197Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 429,284 control chromosomes in the GnomAD database, including 116,838 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.82 (49830 hom., cov: 30)
  • Exomes 𝑓: 0.66 (67008 hom.)
• Consequence: RNF212 NM_001366919.1 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.17
• Publications: 7 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-1058378-A-C is Benign according to our data. Variant chr4-1058378-A-C is described in ClinVar as Benign. ClinVar VariationId is 3047327.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366919.1. 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
	RNF212	NM_001366919.1		c.590T>G	p.Leu197Arg	missense	Exon 10 of 12	NP_001353848.1	A0A8V8TN20
	RNF212	NM_001366918.1		c.590T>G	p.Leu197Arg	missense	Exon 10 of 11	NP_001353847.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	ENST00000698262.1		c.590T>G	p.Leu197Arg	missense	Exon 10 of 12	ENSP00000513634.1	A0A8V8TN20
	RNF212	ENST00000503206.5	TSL:3	n.163T>G		non_coding_transcript_exon	Exon 4 of 5
	RNF212	ENST00000505693.5	TSL:5	n.517T>G		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes AF: 0.822 AC: 118597 AN: 144356 Hom.: 49798 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.771

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.814

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.806

GnomAD4 exome AF: 0.662 AC: 188548 AN: 284816 Hom.: 67008 Cov.: 0 AF XY: 0.660 AC XY: 87053 AN XY: 131838

African (AFR) AF: 0.913 AC: 3557 AN: 3898

American (AMR) AF: 0.503 AC: 191 AN: 380

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 980 AN: 1482

East Asian (EAS) AF: 0.477 AC: 696 AN: 1460

South Asian (SAS) AF: 0.621 AC: 3184 AN: 5124

European-Finnish (FIN) AF: 0.757 AC: 368 AN: 486

Middle Eastern (MID) AF: 0.710 AC: 1144 AN: 1612

European-Non Finnish (NFE) AF: 0.660 AC: 172464 AN: 261174

Other (OTH) AF: 0.648 AC: 5964 AN: 9200

GnomAD4 genome AF: 0.821 AC: 118676 AN: 144468 Hom.: 49830 Cov.: 30 AF XY: 0.818 AC XY: 57545 AN XY: 70362

African (AFR) AF: 0.943 AC: 37940 AN: 40224

American (AMR) AF: 0.690 AC: 9976 AN: 14454

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2594 AN: 3224

East Asian (EAS) AF: 0.638 AC: 2979 AN: 4668

South Asian (SAS) AF: 0.771 AC: 3416 AN: 4430

European-Finnish (FIN) AF: 0.819 AC: 8067 AN: 9852

Middle Eastern (MID) AF: 0.806 AC: 216 AN: 268

European-Non Finnish (NFE) AF: 0.796 AC: 51349 AN: 64496

Other (OTH) AF: 0.805 AC: 1595 AN: 1982

Alfa AF: 0.740 Hom.: 4498

Bravo AF: 0.807

Asia WGS AF: 0.561 AC: 1506 AN: 2680

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	RNF212-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.69
DANN	Benign	0.70
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs2248083; hg19: chr4-1052166;