Genetic Variant RNF212:c.172-4654T>C (chr4-1101493-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001131034.4(RNF212):c.172-4654T>C variant causes a intron change. The variant allele was found at a frequency of 0.568 in 154,574 control chromosomes in the GnomAD database, including 26,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

Frequency

Genomes: 𝑓 0.57 ( 26372 hom., cov: 32)

Exomes 𝑓: 0.67 ( 559 hom. )

Consequence

RNF212
NM_001131034.4 intron

Scores

Clinical Significance

association no assertion criteria provided O:1

Conservation

PhyloP100: 4.45

Publications

39 publications found

Variant links:

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)

RNF212 links:

ENSG00000251639 (HGNC:):

ENSG00000251639 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF212	NM_001131034.4 link	c.172-4654T>C		intron_variant	Intron 2 of 9	ENST00000433731.7	NP_001124506.1	Q495C1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF212	ENST00000433731.7 link	c.172-4654T>C		intron_variant	Intron 2 of 9	1	NM_001131034.4	ENSP00000389709.2		Q495C1-1

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86203

AN:

151974

Hom.:

26385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.479

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.720

Gnomad EAS

AF:

0.609

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.678

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.685

Gnomad OTH

AF:

0.592

GnomAD4 exome

AF:

0.674

AC:

1672

AN:

2482

Hom.:

559

Cov.:

AF XY:

0.668

AC XY:

844

AN XY:

1264

show subpopulations

African (AFR)

AF:

0.385

AC:

AN:

American (AMR)

AF:

0.530

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.652

AC:

AN:

South Asian (SAS)

AF:

0.669

AC:

198

AN:

296

European-Finnish (FIN)

AF:

0.693

AC:

176

AN:

254

Middle Eastern (MID)

AF:

0.800

AC:

AN:

European-Non Finnish (NFE)

AF:

0.686

AC:

1079

AN:

1572

Other (OTH)

AF:

0.606

AC:

AN:

160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

102

127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.567

AC:

86201

AN:

152092

Hom.:

26372

Cov.:

AF XY:

0.568

AC XY:

42211

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.322

AC:

13345

AN:

41450

American (AMR)

AF:

0.559

AC:

8551

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.720

AC:

2499

AN:

3470

East Asian (EAS)

AF:

0.609

AC:

3152

AN:

5178

South Asian (SAS)

AF:

0.628

AC:

3034

AN:

4830

European-Finnish (FIN)

AF:

0.678

AC:

7162

AN:

10566

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.685

AC:

46585

AN:

67992

Other (OTH)

AF:

0.588

AC:

1243

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1737

3473

5210

6946

8683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.647

Hom.:

145484

Bravo

AF:

0.545

Asia WGS

AF:

0.563

AC:

1957

AN:

3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RECOMBINATION RATE QUANTITATIVE TRAIT LOCUS 1

Other:1

Mar 07, 2008

OMIM

Significance:association

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.7

(source)

DANN

Benign

0.46

PhyloP100

4.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over