5-64191091-G-T

Variant summary

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

The NM_001113561.2(RNF180):c.1-9717G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,174 control chromosomes in the GnomAD database, including 887 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 0.10 (887 hom., cov: 32)
• Consequence: RNF180 NM_001113561.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.448

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF180	NM_001113561.2	c.1-9717G>T		intron_variant		ENST00000389100.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF180	ENST00000389100.9	c.1-9717G>T		intron_variant		1	NM_001113561.2	P1
RNF180	ENST00000296615.10	c.1-9717G>T		intron_variant		1
RNF180	ENST00000504296.1	c.1-9717G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15374 AN: 152056 Hom.: 885 Cov.: 32

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0986

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

GnomAD4 genome AF: 0.101 AC: 15384 AN: 152174 Hom.: 887 Cov.: 32 AF XY: 0.0993 AC XY: 7389 AN XY: 74390

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.00173

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0971

Alfa AF: 0.0740 Hom.: 157

Bravo AF: 0.103

Asia WGS AF: 0.0740 AC: 259 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.9
Dann	Benign	0.48

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: rs6880454; hg19: chr5-63486918;