rs2180341

Positions:

• chr6-127279485-G-A

Variant summary

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

The NM_001242850.2(RNF146):​c.-108-746G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 151,512 control chromosomes in the GnomAD database, including 40,581 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 0.73 (40581 hom., cov: 31)
• Consequence: RNF146 NM_001242850.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.03

Genes affected

RNF146 (HGNC:21336): (ring finger protein 146) Enables poly-ADP-D-ribose binding activity and ubiquitin-protein transferase activity. Involved in positive regulation of canonical Wnt signaling pathway; protein ubiquitination; and ubiquitin-dependent protein catabolic process. Located in cytosol; nucleoplasm; and plasma 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF146	NM_001242850.2	c.-108-746G>A		intron_variant		ENST00000368314.6	NP_001229779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF146	ENST00000368314.6	c.-108-746G>A		intron_variant		2	NM_001242850.2	ENSP00000357297	A1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110587 AN: 151394 Hom.: 40555 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.730 AC: 110662 AN: 151512 Hom.: 40581 Cov.: 31 AF XY: 0.725 AC XY: 53641 AN XY: 74010

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.762

Gnomad4 EAS AF: 0.779

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.751

Alfa AF: 0.751 Hom.: 81723

Bravo AF: 0.734

Asia WGS AF: 0.689 AC: 2397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.016
DANN	Benign	0.58

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: rs2180341; hg19: chr6-127600630;