NM_001131034.4:c.247-2861C>T

Variant names:

• chr4-1093699-G-A
• rs60035268
• NM_001131034.4:c.247-2861C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.362
• Publications: 11 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 -20 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 VariationId is 403382.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.175 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.247-2861C>T		intron	N/A	NP_001124506.1	Q495C1-1
	RNF212	NM_001193318.3		c.562C>T	p.Gln188*	stop_gained	Exon 4 of 4	NP_001180247.1	Q495C1-6
	RNF212	NM_001366919.1		c.247-2861C>T		intron	N/A	NP_001353848.1	A0A8V8TN20

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF212	ENST00000433731.7	TSL:1 MANE Select	c.247-2861C>T		intron	N/A	ENSP00000389709.2	Q495C1-1
	RNF212	ENST00000382968.9	TSL:1	c.247-2861C>T		intron	N/A	ENSP00000372428.5	Q495C1-5
	RNF212	ENST00000333673.5	TSL:2	c.562C>T	p.Gln188*	stop_gained	Exon 4 of 4	ENSP00000327481.5	Q495C1-6

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

GnomAD2 exomes AF: 0.109 AC: 14884 AN: 136428 AF XY: 0.109

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 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

African (AFR) AF: 0.0245 AC: 775 AN: 31594

American (AMR) AF: 0.0852 AC: 3040 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.0693 AC: 1744 AN: 25182

East Asian (EAS) AF: 0.000224 AC: 8 AN: 35734

South Asian (SAS) AF: 0.0484 AC: 3837 AN: 79230

European-Finnish (FIN) AF: 0.168 AC: 5701 AN: 33938

Middle Eastern (MID) AF: 0.0420 AC: 239 AN: 5696

European-Non Finnish (NFE) AF: 0.184 AC: 198114 AN: 1078868

Other (OTH) AF: 0.130 AC: 7505 AN: 57908

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

African (AFR) AF: 0.0310 AC: 1289 AN: 41568

American (AMR) AF: 0.0980 AC: 1500 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0738 AC: 256 AN: 3468

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5186

South Asian (SAS) AF: 0.0476 AC: 230 AN: 4830

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10612

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.178 AC: 12093 AN: 68000

Other (OTH) AF: 0.0938 AC: 198 AN: 2110

Alfa AF: 0.148 Hom.: 3282

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.36
Vest4		0.015
GERP RS		1.0
Mutation Taster		=187/13	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: rs60035268; hg19: chr4-1087487; COSMIC: COSV107371769; COSMIC: COSV107371769;