chr4-1074990-A-G

Variant names:

• chr4-1074990-A-G
• rs2014318
• NM_001131034.4:c.511-1328T>C

Variant summary

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

The NM_001131034.4(RNF212):​c.511-1328T>C 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 152,172 control chromosomes in the GnomAD database, including 50,728 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 (50728 hom., cov: 32)
• Consequence: RNF212 NM_001131034.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF212	NM_001131034.4	c.511-1328T>C		intron_variant	Intron 8 of 9	ENST00000433731.7	NP_001124506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000433731.7	c.511-1328T>C		intron_variant	Intron 8 of 9	1	NM_001131034.4	ENSP00000389709.2

Frequencies

GnomAD3 genomes AF: 0.811 AC: 123297 AN: 152054 Hom.: 50692 Cov.: 32

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.804

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: 123384 AN: 152172 Hom.: 50728 Cov.: 32 AF XY: 0.806 AC XY: 59974 AN XY: 74376

African (AFR) AF: 0.940 AC: 39069 AN: 41546

American (AMR) AF: 0.684 AC: 10462 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2719 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3190 AN: 5156

South Asian (SAS) AF: 0.757 AC: 3652 AN: 4824

European-Finnish (FIN) AF: 0.804 AC: 8500 AN: 10572

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

European-Non Finnish (NFE) AF: 0.784 AC: 53313 AN: 67990

Other (OTH) AF: 0.791 AC: 1674 AN: 2116

Alfa AF: 0.776 Hom.: 10018

Bravo AF: 0.806

Asia WGS AF: 0.667 AC: 2320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.41
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: rs2014318; hg19: chr4-1068778;