4-1093083-T-C

Variant names:

• chr4-1093083-T-C
• rs11939380
• NM_001131034.4:c.247-2245A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001131034.4(RNF212):​c.247-2245A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.58 (27038 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: RNF212 NM_001131034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF212	NM_001131034.4	c.247-2245A>G		intron_variant	Intron 3 of 9	ENST00000433731.7	NP_001124506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000433731.7	c.247-2245A>G		intron_variant	Intron 3 of 9	1	NM_001131034.4	ENSP00000389709.2

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87716 AN: 151720 Hom.: 27043 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.607

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

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.578 AC: 87736 AN: 151838 Hom.: 27038 Cov.: 32 AF XY: 0.579 AC XY: 42966 AN XY: 74182

African (AFR) AF: 0.352 AC: 14560 AN: 41358

American (AMR) AF: 0.564 AC: 8610 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2499 AN: 3470

East Asian (EAS) AF: 0.617 AC: 3174 AN: 5144

South Asian (SAS) AF: 0.688 AC: 3311 AN: 4812

European-Finnish (FIN) AF: 0.677 AC: 7148 AN: 10552

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46526 AN: 67928

Other (OTH) AF: 0.608 AC: 1277 AN: 2102

Alfa AF: 0.584 Hom.: 7363

Bravo AF: 0.556

Asia WGS AF: 0.605 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.3
DANN	Benign	0.78
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11939380; hg19: chr4-1086871;