Genetic Variant NM_018683.4: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:

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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

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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