chr4-1078432-C-T

Variant names:

• chr4-1078432-C-T
• rs1466215
• NM_001131034.4:c.510+1211G>A

Variant summary

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

The NM_001131034.4(RNF212):​c.510+1211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 151,960 control chromosomes in the GnomAD database, including 26,291 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 0.57 (26291 hom., cov: 31)
• Consequence: RNF212 NM_001131034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.679 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	NM_001131034.4	MANE Select	c.510+1211G>A		intron	N/A	NP_001124506.1	Q495C1-1
	RNF212	NM_001366919.1		c.510+1211G>A		intron	N/A	NP_001353848.1	A0A8V8TN20
	RNF212	NM_194439.5		c.510+1211G>A		intron	N/A	NP_919420.1	Q495C1-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	ENST00000433731.7	TSL:1 MANE Select	c.510+1211G>A		intron	N/A	ENSP00000389709.2	Q495C1-1
	RNF212	ENST00000382968.9	TSL:1	c.510+1211G>A		intron	N/A	ENSP00000372428.5	Q495C1-5
	RNF212	ENST00000698262.1		c.510+1211G>A		intron	N/A	ENSP00000513634.1	A0A8V8TN20

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85919 AN: 151842 Hom.: 26306 Cov.: 31

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.611

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.565 AC: 85917 AN: 151960 Hom.: 26291 Cov.: 31 AF XY: 0.567 AC XY: 42082 AN XY: 74268

African (AFR) AF: 0.318 AC: 13165 AN: 41430

American (AMR) AF: 0.558 AC: 8517 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2500 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3150 AN: 5162

South Asian (SAS) AF: 0.632 AC: 3044 AN: 4814

European-Finnish (FIN) AF: 0.678 AC: 7159 AN: 10564

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.685 AC: 46515 AN: 67940

Other (OTH) AF: 0.588 AC: 1240 AN: 2108

Alfa AF: 0.574 Hom.: 6061

Bravo AF: 0.544

Asia WGS AF: 0.562 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.59
PhyloP100		-0.45
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: rs1466215; hg19: chr4-1072220;