22-31183247-C-T

Position:

• chr22-31183247-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152267.4(RNF185):​c.-48-3800C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,108 control chromosomes in the GnomAD database, including 48,630 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 0.79 (48630 hom., cov: 31)
• Consequence: RNF185 NM_152267.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF185	NM_152267.4	c.-48-3800C>T		intron_variant		ENST00000326132.11	NP_689480.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF185	ENST00000326132.11	c.-48-3800C>T		intron_variant		1	NM_152267.4	ENSP00000320508	P1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120327 AN: 151990 Hom.: 48576 Cov.: 31

Gnomad AFR AF: 0.947

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.807

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.808

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.792 AC: 120436 AN: 152108 Hom.: 48630 Cov.: 31 AF XY: 0.790 AC XY: 58755 AN XY: 74364

Gnomad4 AFR AF: 0.947

Gnomad4 AMR AF: 0.762

Gnomad4 ASJ AF: 0.807

Gnomad4 EAS AF: 0.883

Gnomad4 SAS AF: 0.788

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.810

Alfa AF: 0.741 Hom.: 14843

Bravo AF: 0.805

Asia WGS AF: 0.861 AC: 2992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.63

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

LitVar

Other links and lift over

dbSNP: rs1034589; hg19: chr22-31579233;