Genetic Variant RNF180:c.1-91G>A (chr5-64200717-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_001113561.2(RNF180):c.1-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0967 in 1,088,848 control chromosomes in the GnomAD database, including 5,858 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 0.076 ( 636 hom., cov: 32)

Exomes 𝑓: 0.10 ( 5222 hom. )

Consequence

RNF180
NM_001113561.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.697

Publications

6 publications found

Variant links:

Genes affected

RNF180 (HGNC:27752): (ring finger protein 180) Predicted to enable ubiquitin conjugating enzyme binding activity and ubiquitin protein ligase activity. Predicted to be involved in norepinephrine metabolic process; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and serotonin metabolic process. Predicted to act upstream of or within several processes, including adult behavior; positive regulation of protein ubiquitination; and protein polyubiquitination. Predicted to be located in nuclear envelope. Predicted to be integral component of membrane. Predicted to be intrinsic component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF180 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113561.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RNF180	NM_001113561.2	MANE Select	c.1-91G>A	intron	N/A	NP_001107033.1	Q86T96-1
RNF180	NM_001323292.2		c.1-91G>A	intron	N/A	NP_001310221.1
RNF180	NM_178532.4		c.1-91G>A	intron	N/A	NP_848627.1	Q86T96-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RNF180	ENST00000389100.9	TSL:1 MANE Select	c.1-91G>A	intron	N/A	ENSP00000373752.4	Q86T96-1
RNF180	ENST00000296615.10	TSL:1	c.1-91G>A	intron	N/A	ENSP00000296615.6	Q86T96-2
RNF180	ENST00000876163.1		c.1-91G>A	intron	N/A	ENSP00000546222.1

Frequencies

GnomAD3 genomes

AF:

0.0765

AC:

11634

AN:

152098

Hom.:

639

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0197

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.0670

Gnomad ASJ

AF:

0.0802

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0550

Gnomad FIN

AF:

0.0950

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.0755

GnomAD4 exome

AF:

0.100

AC:

93692

AN:

936632

Hom.:

5222

AF XY:

0.0988

AC XY:

47163

AN XY:

477234

show subpopulations

African (AFR)

AF:

0.0177

AC:

393

AN:

22204

American (AMR)

AF:

0.0494

AC:

1606

AN:

32532

Ashkenazi Jewish (ASJ)

AF:

0.0906

AC:

1674

AN:

18470

East Asian (EAS)

AF:

0.000280

AC:

AN:

35706

South Asian (SAS)

AF:

0.0577

AC:

3588

AN:

62172

European-Finnish (FIN)

AF:

0.0950

AC:

3950

AN:

41568

Middle Eastern (MID)

AF:

0.0760

AC:

229

AN:

3012

European-Non Finnish (NFE)

AF:

0.116

AC:

78435

AN:

678880

Other (OTH)

AF:

0.0905

AC:

3807

AN:

42088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3929

7858

11786

15715

19644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2298

4596

6894

9192

11490

<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:

0.0764

AC:

11627

AN:

152216

Hom.:

636

Cov.:

AF XY:

0.0748

AC XY:

5570

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0197

AC:

818

AN:

41548

American (AMR)

AF:

0.0670

AC:

1024

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0802

AC:

278

AN:

3468

East Asian (EAS)

AF:

0.000578

AC:

AN:

5188

South Asian (SAS)

AF:

0.0547

AC:

264

AN:

4828

European-Finnish (FIN)

AF:

0.0950

AC:

1006

AN:

10584

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7866

AN:

67984

Other (OTH)

AF:

0.0747

AC:

158

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

561

1122

1683

2244

2805

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

130

260

390

520

650

<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:

0.0916

Hom.:

1162

Bravo

AF:

0.0718

Asia WGS

AF:

0.0250

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.48

(source)

DANN

Benign

0.64

PhyloP100

-0.70

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over