4-1075031-G-A

Variant names:

• chr4-1075031-G-A
• rs1010342
• NM_001131034.4:c.511-1369C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001131034.4(RNF212):​c.511-1369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,184 control chromosomes in the GnomAD database, including 48,468 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 0.79 (48468 hom., cov: 33)
• Consequence: RNF212 NM_001131034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001131034.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	NM_001131034.4	MANE Select	c.511-1369C>T		intron	N/A	NP_001124506.1
	RNF212	NM_001366919.1		c.511-1369C>T		intron	N/A	NP_001353848.1
	RNF212	NM_194439.5		c.511-1369C>T		intron	N/A	NP_919420.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	ENST00000433731.7	TSL:1 MANE Select	c.511-1369C>T		intron	N/A	ENSP00000389709.2
	RNF212	ENST00000382968.9	TSL:1	c.511-1369C>T		intron	N/A	ENSP00000372428.5
	RNF212	ENST00000698262.1		c.511-1369C>T		intron	N/A	ENSP00000513634.1

Frequencies

GnomAD3 genomes AF: 0.795 AC: 120823 AN: 152066 Hom.: 48451 Cov.: 33

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.804

Gnomad MID AF: 0.794

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: 0.794 AC: 120887 AN: 152184 Hom.: 48468 Cov.: 33 AF XY: 0.791 AC XY: 58824 AN XY: 74390

African (AFR) AF: 0.884 AC: 36715 AN: 41548

American (AMR) AF: 0.678 AC: 10357 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2714 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3189 AN: 5152

South Asian (SAS) AF: 0.757 AC: 3649 AN: 4820

European-Finnish (FIN) AF: 0.804 AC: 8508 AN: 10586

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.784 AC: 53301 AN: 68008

Other (OTH) AF: 0.782 AC: 1651 AN: 2112

Alfa AF: 0.779 Hom.: 60380

Bravo AF: 0.787

Asia WGS AF: 0.662 AC: 2303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1010342; hg19: chr4-1068819;