4-1056848-C-T

Variant names:

• chr4-1056848-C-T
• rs60085185
• NM_001366919.1:c.804G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001366919.1(RNF212):​c.804G>A​(p.Arg268Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 987,466 control chromosomes in the GnomAD database, including 12,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (6469 hom., cov: 33)
  • Exomes 𝑓: 0.099 (5970 hom.)
• Consequence: RNF212 NM_001366919.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.144
• Publications: 2 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)

ENSG00000294272 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 4-1056848-C-T is Benign according to our data. Variant chr4-1056848-C-T is described in ClinVar as Benign. ClinVar VariationId is 3031982.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.144 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.523 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.804G>A	p.Arg268Arg	synonymous	Exon 11 of 12	NP_001353848.1	A0A8V8TN20
	RNF212	NM_001366918.1		c.648-345G>A		intron	N/A	NP_001353847.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	ENST00000698262.1		c.804G>A	p.Arg268Arg	synonymous	Exon 11 of 12	ENSP00000513634.1	A0A8V8TN20
	RNF212	ENST00000505693.5	TSL:5	n.731G>A		non_coding_transcript_exon	Exon 5 of 6
	RNF212	ENST00000514024.5	TSL:2	n.264G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32592 AN: 152048 Hom.: 6456 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.0992 AC: 82856 AN: 835300 Hom.: 5970 Cov.: 27 AF XY: 0.0984 AC XY: 37962 AN XY: 385870

African (AFR) AF: 0.560 AC: 8864 AN: 15838

American (AMR) AF: 0.0877 AC: 87 AN: 992

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 379 AN: 5154

East Asian (EAS) AF: 0.000551 AC: 2 AN: 3630

South Asian (SAS) AF: 0.0782 AC: 1294 AN: 16546

European-Finnish (FIN) AF: 0.0955 AC: 60 AN: 628

Middle Eastern (MID) AF: 0.0757 AC: 243 AN: 3210

European-Non Finnish (NFE) AF: 0.0906 AC: 69024 AN: 761828

Other (OTH) AF: 0.106 AC: 2903 AN: 27474

GnomAD4 genome AF: 0.215 AC: 32644 AN: 152166 Hom.: 6469 Cov.: 33 AF XY: 0.210 AC XY: 15591 AN XY: 74396

African (AFR) AF: 0.529 AC: 21939 AN: 41456

American (AMR) AF: 0.113 AC: 1727 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5172

South Asian (SAS) AF: 0.0682 AC: 329 AN: 4824

European-Finnish (FIN) AF: 0.126 AC: 1335 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0959 AC: 6522 AN: 68024

Other (OTH) AF: 0.173 AC: 365 AN: 2106

Alfa AF: 0.158 Hom.: 1200

Bravo AF: 0.228

Asia WGS AF: 0.0610 AC: 213 AN: 3478

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	-0.48
CADD	Benign	3.6
DANN	Benign	0.69
PhyloP100		0.14

Splicing

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

Other links and lift over

dbSNP: rs60085185; hg19: chr4-1050636;