rs60035268

chr4-1093699-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001131034.4(RNF212):c.247-2861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,536,132 control chromosomes in the GnomAD database, including 21,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1346 hom., cov: 33)
  • Exomes 𝑓: 0.16 (19783 hom.)
• Consequence: RNF212 NM_001131034.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.362

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.879525).
• BP6: Variant 4-1093699-G-A is Benign according to our data. Variant chr4-1093699-G-A is described in ClinVar as [Benign]. Clinvar id is 403382.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF212	NM_001131034.4	c.247-2861C>T		intron_variant		ENST00000433731.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF212	ENST00000433731.7	c.247-2861C>T		intron_variant		1	NM_001131034.4	A2

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17496 AN: 152164 Hom.: 1347 Cov.: 33

Gnomad AFR AF: 0.0311

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.0738

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.0948

GnomAD3 exomes AF: 0.109 AC: 14884 AN: 136428 Hom.: 1149 AF XY: 0.109 AC XY: 8076 AN XY: 74170

Gnomad AFR exome AF: 0.0290

Gnomad AMR exome AF: 0.0834

Gnomad ASJ exome AF: 0.0692

Gnomad EAS exome AF: 0.000190

Gnomad SAS exome AF: 0.0482

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.176

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.160 AC: 220963 AN: 1383850 Hom.: 19783 Cov.: 54 AF XY: 0.157 AC XY: 106884 AN XY: 682870

Gnomad4 AFR exome AF: 0.0245

Gnomad4 AMR exome AF: 0.0852

Gnomad4 ASJ exome AF: 0.0693

Gnomad4 EAS exome AF: 0.000224

Gnomad4 SAS exome AF: 0.0484

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.130

GnomAD4 genome AF: 0.115 AC: 17492 AN: 152282 Hom.: 1346 Cov.: 33 AF XY: 0.112 AC XY: 8372 AN XY: 74464

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.0980

Gnomad4 ASJ AF: 0.0738

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0476

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.155 Hom.: 2581

Bravo AF: 0.106

TwinsUK AF: 0.179 AC: 663

ALSPAC AF: 0.183 AC: 705

ExAC AF: 0.0659 AC: 1382

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 150/2178=6.8% -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.88	T
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.4
Dann	Benign	0.96
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.016	N
MutationTaster	Benign	0.000011	P;P;P
Vest4		0.015
GERP RS		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs60035268; hg19: chr4-1087487;