Genetic Variant NM_001199383.2:c.*687G>A (chr5-159157983-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001199383.2(RNF145):c.*687G>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 0.863 in 152,766 control chromosomes in the GnomAD database, including 57,341 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 0.86 ( 57185 hom., cov: 31)

Exomes 𝑓: 0.76 ( 156 hom. )

Consequence

RNF145
NM_001199383.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0140

Publications

15 publications found

Variant links:

Genes affected

RNF145 (HGNC:20853): (ring finger protein 145) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

RNF145 links:

LINC02202 (HGNC:53068): (long intergenic non-protein coding RNA 2202)

LINC02202 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=-0.49).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199383.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RNF145	NM_001199383.2	MANE Select	c.*687G>A	3_prime_UTR	Exon 11 of 11	NP_001186312.1
RNF145	NM_001199380.2		c.*687G>A	3_prime_UTR	Exon 11 of 11	NP_001186309.1
RNF145	NM_144726.3		c.*687G>A	3_prime_UTR	Exon 11 of 11	NP_653327.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RNF145	ENST00000424310.7	TSL:1 MANE Select	c.*687G>A	3_prime_UTR	Exon 11 of 11	ENSP00000409064.2
RNF145	ENST00000274542.6	TSL:2	c.*687G>A	3_prime_UTR	Exon 11 of 11	ENSP00000274542.2
RNF145	ENST00000519865.5	TSL:5	c.*687G>A	3_prime_UTR	Exon 11 of 11	ENSP00000430397.1

Frequencies

GnomAD3 genomes

AF:

0.864

AC:

131368

AN:

152098

Hom.:

57132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.961

Gnomad AMI

AF:

0.897

Gnomad AMR

AF:

0.885

Gnomad ASJ

AF:

0.806

Gnomad EAS

AF:

0.907

Gnomad SAS

AF:

0.919

Gnomad FIN

AF:

0.759

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.811

Gnomad OTH

AF:

0.859

GnomAD4 exome

AF:

0.764

AC:

422

AN:

552

Hom.:

156

Cov.:

AF XY:

0.764

AC XY:

249

AN XY:

326

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.828

AC:

106

AN:

128

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.740

AC:

296

AN:

400

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.813

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

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:

0.864

AC:

131477

AN:

152214

Hom.:

57185

Cov.:

AF XY:

0.864

AC XY:

64267

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.961

AC:

39952

AN:

41558

American (AMR)

AF:

0.885

AC:

13534

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.806

AC:

2796

AN:

3470

East Asian (EAS)

AF:

0.907

AC:

4694

AN:

5176

South Asian (SAS)

AF:

0.919

AC:

4431

AN:

4820

European-Finnish (FIN)

AF:

0.759

AC:

8024

AN:

10572

Middle Eastern (MID)

AF:

0.871

AC:

256

AN:

294

European-Non Finnish (NFE)

AF:

0.811

AC:

55162

AN:

68002

Other (OTH)

AF:

0.856

AC:

1810

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

914

1829

2743

3658

4572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.834

Hom.:

133827

Bravo

AF:

0.875

Asia WGS

AF:

0.902

AC:

3138

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.8

(source)

DANN

Benign

0.83

PhyloP100

0.014

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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