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GeneBe

22-31192690-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_152267.4(RNF185):c.183G>A(p.Pro61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,613,726 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 4 hom., cov: 32)
Exomes 𝑓: 0.0015 ( 25 hom. )

Consequence

RNF185
NM_152267.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.81
Variant links:
Genes affected
RNF185 (HGNC:26783): (ring finger protein 185) Enables ubiquitin binding activity; ubiquitin protein ligase activity; and ubiquitin-like protein conjugating enzyme binding activity. Involved in positive regulation of ERAD pathway; protein autoubiquitination; and ubiquitin-dependent ERAD pathway. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-31192690-G-A is Benign according to our data. Variant chr22-31192690-G-A is described in ClinVar as [Benign]. Clinvar id is 779392.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.81 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00145 (2121/1461510) while in subpopulation AMR AF= 0.0298 (1334/44702). AF 95% confidence interval is 0.0285. There are 25 homozygotes in gnomad4_exome. There are 872 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RNF185NM_152267.4 linkuse as main transcriptc.183G>A p.Pro61= synonymous_variant 3/7 ENST00000326132.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RNF185ENST00000326132.11 linkuse as main transcriptc.183G>A p.Pro61= synonymous_variant 3/71 NM_152267.4 P1Q96GF1-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00210
AC:
319
AN:
152098
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000507
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0159
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00637
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000176
Gnomad OTH
AF:
0.00479
GnomAD3 exomes
AF:
0.00515
AC:
1296
AN:
251422
Hom.:
22
AF XY:
0.00385
AC XY:
523
AN XY:
135890
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.0319
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00729
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000211
Gnomad OTH exome
AF:
0.00489
GnomAD4 exome
AF:
0.00145
AC:
2121
AN:
1461510
Hom.:
25
Cov.:
29
AF XY:
0.00120
AC XY:
872
AN XY:
727102
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.0298
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0125
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000173
Gnomad4 OTH exome
AF:
0.00142
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00208
AC:
317
AN:
152216
Hom.:
4
Cov.:
32
AF XY:
0.00200
AC XY:
149
AN XY:
74418
show subpopulations
Gnomad4 AFR
AF:
0.000506
Gnomad4 AMR
AF:
0.0158
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00638
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000176
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.000505
Hom.:
0
Bravo
AF:
0.00449
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 29, 2017- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.72
Cadd
Benign
9.3
Dann
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs118153223; hg19: chr22-31588676; API