6-127266770-T-G

Position:

• chr6-127266770-T-G

Variant summary

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

The NM_001242851.1(RNF146):​c.-109+61T>G variant causes a intron 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 NM_001242851.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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]

RNF146 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
RNF146	NM_001242851.1	c.-109+61T>G		intron_variant			NP_001229780.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF146	ENST00000476956.5	n.45T>G		non_coding_transcript_exon_variant	1/4	2

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

Gnomad4 EAS exome AF: 1.00

Gnomad4 NFE exome AF: 0.938

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

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.624

Gnomad4 FIN AF: 0.728

Gnomad4 NFE AF: 0.758

Gnomad4 OTH AF: 0.752

Alfa AF: 0.679 Hom.: 2018

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs877661; hg19: chr6-127587915;