6-127266770-T-G

Variant names:

• chr6-127266770-T-G
• rs877661
• ENST00000476956.5:n.45T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000476956.5(RNF146):​n.45T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 151,702 control chromosomes in the GnomAD database, including 41,055 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 (41046 hom., cov: 29)
  • Exomes 𝑓: 0.95 (9 hom.)
• Consequence: RNF146 ENST00000476956.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNF146	NM_001242850.2	c.-264T>G		upstream_gene_variant		ENST00000368314.6	NP_001229779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF146	ENST00000368314.6	c.-264T>G		upstream_gene_variant		2	NM_001242850.2	ENSP00000357297.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111298 AN: 151574 Hom.: 41024 Cov.: 29

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.625

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.758

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.950 AC: 19 AN: 20 Hom.: 9 Cov.: 0 AF XY: 0.950 AC XY: 19 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 4 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.938 AC: 15 AN: 16

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.734 AC: 111364 AN: 151682 Hom.: 41046 Cov.: 29 AF XY: 0.729 AC XY: 54014 AN XY: 74102

African (AFR) AF: 0.694 AC: 28678 AN: 41350

American (AMR) AF: 0.753 AC: 11498 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.772 AC: 2679 AN: 3470

East Asian (EAS) AF: 0.780 AC: 3974 AN: 5094

South Asian (SAS) AF: 0.624 AC: 2997 AN: 4800

European-Finnish (FIN) AF: 0.728 AC: 7663 AN: 10524

Middle Eastern (MID) AF: 0.743 AC: 217 AN: 292

European-Non Finnish (NFE) AF: 0.758 AC: 51424 AN: 67876

Other (OTH) AF: 0.752 AC: 1583 AN: 2104

Alfa AF: 0.682 Hom.: 2212

Bravo AF: 0.737

Asia WGS AF: 0.692 AC: 2410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.33
PhyloP100		-1.6
PromoterAI		0.011	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs877661; hg19: chr6-127587915;