6-127285443-T-C

Variant names:

• chr6-127285443-T-C
• rs6569479
• NM_001242850.2:c.3-1173T>C

Variant summary

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

The NM_001242850.2(RNF146):​c.3-1173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 573,868 control chromosomes in the GnomAD database, including 160,273 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 (40486 hom., cov: 29)
  • Exomes 𝑓: 0.75 (119787 hom.)
• Consequence: RNF146 NM_001242850.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 15 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=-1.04).
• 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 rank	MANE	Protein	UniProt
RNF146	NM_001242850.2	c.3-1173T>C		intron_variant	Intron 2 of 2	ENST00000368314.6	NP_001229779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNF146	ENST00000368314.6	c.3-1173T>C		intron_variant	Intron 2 of 2	2	NM_001242850.2	ENSP00000357297.1

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110350 AN: 151156 Hom.: 40460 Cov.: 29

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.762

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.620

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.753 AC: 318393 AN: 422596 Hom.: 119787 AF XY: 0.752 AC XY: 150110 AN XY: 199720

African (AFR) AF: 0.678 AC: 5163 AN: 7620

American (AMR) AF: 0.719 AC: 318 AN: 442

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2041 AN: 2636

East Asian (EAS) AF: 0.783 AC: 1344 AN: 1716

South Asian (SAS) AF: 0.645 AC: 5244 AN: 8132

European-Finnish (FIN) AF: 0.773 AC: 102 AN: 132

Middle Eastern (MID) AF: 0.697 AC: 584 AN: 838

European-Non Finnish (NFE) AF: 0.757 AC: 293221 AN: 387214

Other (OTH) AF: 0.748 AC: 10376 AN: 13866

GnomAD4 genome AF: 0.730 AC: 110424 AN: 151272 Hom.: 40486 Cov.: 29 AF XY: 0.724 AC XY: 53479 AN XY: 73840

African (AFR) AF: 0.690 AC: 28442 AN: 41232

American (AMR) AF: 0.751 AC: 11386 AN: 15156

Ashkenazi Jewish (ASJ) AF: 0.762 AC: 2637 AN: 3460

East Asian (EAS) AF: 0.780 AC: 3979 AN: 5104

South Asian (SAS) AF: 0.620 AC: 2975 AN: 4802

European-Finnish (FIN) AF: 0.723 AC: 7539 AN: 10432

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51014 AN: 67784

Other (OTH) AF: 0.753 AC: 1580 AN: 2098

Alfa AF: 0.734 Hom.: 7814

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	1.7
DANN	Benign	0.54
PhyloP100		-0.80
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: rs6569479; hg19: chr6-127606588;