rs11949052

Positions:

• chr5-64200717-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697

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=-0.85).
• 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/exons	MANE	Protein	UniProt
RNF180	NM_001113561.2	c.1-91G>A		intron_variant		ENST00000389100.9	NP_001107033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF180	ENST00000389100.9	c.1-91G>A		intron_variant		1	NM_001113561.2	ENSP00000373752.4
RNF180	ENST00000296615.10	c.1-91G>A		intron_variant		1		ENSP00000296615.6
RNF180	ENST00000504296.1	c.1-91G>A		intron_variant		3		ENSP00000426884.1

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11634 AN: 152098 Hom.: 639 Cov.: 32

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

Gnomad4 AFR exome AF: 0.0177

Gnomad4 AMR exome AF: 0.0494

Gnomad4 ASJ exome AF: 0.0906

Gnomad4 EAS exome AF: 0.000280

Gnomad4 SAS exome AF: 0.0577

Gnomad4 FIN exome AF: 0.0950

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.0905

GnomAD4 genome AF: 0.0764 AC: 11627 AN: 152216 Hom.: 636 Cov.: 32 AF XY: 0.0748 AC XY: 5570 AN XY: 74432

Gnomad4 AFR AF: 0.0197

Gnomad4 AMR AF: 0.0670

Gnomad4 ASJ AF: 0.0802

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0547

Gnomad4 FIN AF: 0.0950

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0747

Alfa AF: 0.102 Hom.: 868

Bravo AF: 0.0718

Asia WGS AF: 0.0250 AC: 86 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
DANN	Benign	0.64

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: rs11949052; hg19: chr5-63496544;