4-1059384-T-C

Variant names:

• chr4-1059384-T-C
• rs6839931
• NM_001366919.1:c.575-991A>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.575-991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 152,264 control chromosomes in the GnomAD database, including 50,809 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 0.81 (50809 hom., cov: 34)
• Consequence: RNF212 NM_001366919.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 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.575-991A>G		intron	N/A	NP_001353848.1	A0A8V8TN20
	RNF212	NM_001366918.1		c.575-991A>G		intron	N/A	NP_001353847.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	ENST00000698262.1		c.575-991A>G		intron	N/A	ENSP00000513634.1	A0A8V8TN20
	RNF212	ENST00000503206.5	TSL:3	n.148-991A>G		intron	N/A
	RNF212	ENST00000505693.5	TSL:5	n.502-991A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123421 AN: 152146 Hom.: 50773 Cov.: 34

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.784

Gnomad OTH AF: 0.793

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

GnomAD4 genome AF: 0.811 AC: 123508 AN: 152264 Hom.: 50809 Cov.: 34 AF XY: 0.807 AC XY: 60057 AN XY: 74444

African (AFR) AF: 0.941 AC: 39129 AN: 41570

American (AMR) AF: 0.685 AC: 10478 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2720 AN: 3472

East Asian (EAS) AF: 0.618 AC: 3203 AN: 5180

South Asian (SAS) AF: 0.757 AC: 3655 AN: 4830

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

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53319 AN: 67996

Other (OTH) AF: 0.791 AC: 1671 AN: 2112

Alfa AF: 0.817 Hom.: 13450

Bravo AF: 0.807

Asia WGS AF: 0.667 AC: 2320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs6839931; hg19: chr4-1053172;