Genetic Variant NM_001113561.2: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:

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=-0.85).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF180	NM_001113561.2 link	c.1-91G>A		intron_variant	Intron 1 of 7	ENST00000389100.9	NP_001107033.1	Q86T96-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RNF180	ENST00000389100.9 link	c.1-91G>A	intron_variant	Intron 1 of 7	1	NM_001113561.2	ENSP00000373752.4	Q86T96-1
RNF180	ENST00000296615.10 link	c.1-91G>A	intron_variant	Intron 1 of 4	1		ENSP00000296615.6	Q86T96-2
RNF180	ENST00000504296.1 link	c.1-91G>A	intron_variant	Intron 1 of 3	3		ENSP00000426884.1	D6RE88

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over