rs2180341

Variant names:

• chr6-127279485-G-A
• rs2180341
• NM_001242850.2:c.-108-746G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 91 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242850.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF146	NM_001242850.2	MANE Select	c.-108-746G>A		intron	N/A	NP_001229779.1	Q9NTX7-1
	RNF146	NM_001242849.2		c.-108-746G>A		intron	N/A	NP_001229778.1	Q9NTX7-1
	RNF146	NM_001242851.1		c.-108-746G>A		intron	N/A	NP_001229780.1	Q9NTX7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNF146	ENST00000368314.6	TSL:2 MANE Select	c.-108-746G>A		intron	N/A	ENSP00000357297.1	Q9NTX7-1
	RNF146	ENST00000911118.1		c.-854G>A		5_prime_UTR	Exon 1 of 2	ENSP00000581177.1
	RNF146	ENST00000610153.1	TSL:2	c.-108-746G>A		intron	N/A	ENSP00000476814.1	Q9NTX7-1

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

African (AFR) AF: 0.691 AC: 28565 AN: 41366

American (AMR) AF: 0.752 AC: 11436 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2636 AN: 3460

East Asian (EAS) AF: 0.779 AC: 3995 AN: 5128

South Asian (SAS) AF: 0.620 AC: 2982 AN: 4812

European-Finnish (FIN) AF: 0.725 AC: 7629 AN: 10526

Middle Eastern (MID) AF: 0.736 AC: 215 AN: 292

European-Non Finnish (NFE) AF: 0.753 AC: 50967 AN: 67702

Other (OTH) AF: 0.751 AC: 1581 AN: 2104

Alfa AF: 0.748 Hom.: 186346

Bravo AF: 0.734

Asia WGS AF: 0.689 AC: 2397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.016
DANN	Benign	0.58
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2180341; hg19: chr6-127600630;