dbSNP rs2235616: RNF114:c.*449G>A (chr20-49952590-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018683.4(RNF114):c.*449G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 231,308 control chromosomes in the GnomAD database, including 18,340 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 0.35 ( 11076 hom., cov: 32)

Exomes 𝑓: 0.42 ( 7264 hom. )

Consequence

RNF114
NM_018683.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.62

Publications

18 publications found

Variant links:

Genes affected

RNF114 (HGNC:13094): (ring finger protein 114) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein polyubiquitination and ubiquitin-dependent protein catabolic process. Located in cytosol and plasma membrane. Biomarker of male infertility. [provided by Alliance of Genome Resources, Apr 2022]

RNF114 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=-0.82).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF114	NM_018683.4 link	c.*449G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000244061.6	NP_061153.1	Q9Y508-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF114	ENST00000244061.6 link	c.*449G>A	3_prime_UTR_variant	Exon 6 of 6	1	NM_018683.4	ENSP00000244061.2	Q9Y508-1
RNF114	ENST00000622999.3 link	n.*964G>A	non_coding_transcript_exon_variant	Exon 6 of 6	2		ENSP00000485203.1	A0A096LNT1
RNF114	ENST00000622920.1 link	c.*348G>A	3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000485317.1	A0A096LP02
RNF114	ENST00000622999.3 link	n.*964G>A	3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000485203.1	A0A096LNT1

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53242

AN:

151960

Hom.:

11060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.126

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.340

Gnomad SAS

AF:

0.557

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.358

GnomAD4 exome

AF:

0.420

AC:

33250

AN:

79230

Hom.:

7264

Cov.:

AF XY:

0.423

AC XY:

16982

AN XY:

40172

show subpopulations

African (AFR)

AF:

0.138

AC:

422

AN:

3066

American (AMR)

AF:

0.463

AC:

1672

AN:

3614

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1044

AN:

3148

East Asian (EAS)

AF:

0.356

AC:

2217

AN:

6228

South Asian (SAS)

AF:

0.592

AC:

1187

AN:

2004

European-Finnish (FIN)

AF:

0.575

AC:

2655

AN:

4616

Middle Eastern (MID)

AF:

0.341

AC:

135

AN:

396

European-Non Finnish (NFE)

AF:

0.428

AC:

21816

AN:

50926

Other (OTH)

AF:

0.402

AC:

2102

AN:

5232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

919

1837

2756

3674

4593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.350

AC:

53292

AN:

152078

Hom.:

11076

Cov.:

AF XY:

0.364

AC XY:

27094

AN XY:

74358

show subpopulations

African (AFR)

AF:

0.126

AC:

5220

AN:

41494

American (AMR)

AF:

0.441

AC:

6734

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

1136

AN:

3470

East Asian (EAS)

AF:

0.341

AC:

1764

AN:

5168

South Asian (SAS)

AF:

0.559

AC:

2692

AN:

4820

European-Finnish (FIN)

AF:

0.563

AC:

5968

AN:

10592

Middle Eastern (MID)

AF:

0.320

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28639

AN:

67956

Other (OTH)

AF:

0.359

AC:

758

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1635

3270

4906

6541

8176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

518

1036

1554

2072

2590

<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:

0.388

Hom.:

15591

Bravo

AF:

0.324

Asia WGS

AF:

0.458

AC:

1594

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.54

(source)

DANN

Benign

0.66

PhyloP100

-1.6

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over