rs2511841

Positions:

• chr11-119335665-G-A
• chr11-119335665-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032015.5(RNF26):​c.543G>A​(p.Thr181Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,613,754 control chromosomes in the GnomAD database, including 389,874 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 0.70 (37484 hom., cov: 34)
  • Exomes 𝑓: 0.69 (352390 hom.)
• Consequence: RNF26 NM_032015.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.05

Genes affected

RNF26 (HGNC:14646): (ring finger protein 26) The protein encoded by this intronless gene contains a C3HC5 type of RING finger, a motif known to be involved in protein-DNA and protein-protein interactions. The expression of this gene was found to be upregulated in cancer cell lines derived from different types of cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-4.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF26	NM_032015.5	c.543G>A	p.Thr181Thr	synonymous_variant	1/1	ENST00000311413.5	NP_114404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF26	ENST00000311413.5	c.543G>A	p.Thr181Thr	synonymous_variant	1/1	6	NM_032015.5	ENSP00000312439.4

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106590 AN: 152092 Hom.: 37462 Cov.: 34

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.687

Gnomad OTH AF: 0.679

GnomAD3 exomes AF: 0.720 AC: 180646 AN: 250934 Hom.: 65782 AF XY: 0.719 AC XY: 97530 AN XY: 135648

Gnomad AFR exome AF: 0.714

Gnomad AMR exome AF: 0.838

Gnomad ASJ exome AF: 0.596

Gnomad EAS exome AF: 0.640

Gnomad SAS exome AF: 0.804

Gnomad FIN exome AF: 0.708

Gnomad NFE exome AF: 0.689

Gnomad OTH exome AF: 0.698

GnomAD4 exome AF: 0.693 AC: 1012873 AN: 1461544 Hom.: 352390 Cov.: 75 AF XY: 0.696 AC XY: 505748 AN XY: 727032

Gnomad4 AFR exome AF: 0.710

Gnomad4 AMR exome AF: 0.827

Gnomad4 ASJ exome AF: 0.598

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.799

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.682

Gnomad4 OTH exome AF: 0.681

GnomAD4 genome AF: 0.701 AC: 106656 AN: 152210 Hom.: 37484 Cov.: 34 AF XY: 0.703 AC XY: 52313 AN XY: 74396

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.614

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.803

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.687

Gnomad4 OTH AF: 0.677

Alfa AF: 0.685 Hom.: 88735

Bravo AF: 0.701

Asia WGS AF: 0.725 AC: 2517 AN: 3478

EpiCase AF: 0.674

EpiControl AF: 0.676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.040
DANN	Benign	0.85

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: rs2511841; hg19: chr11-119206375; COSMIC: COSV60991676; COSMIC: COSV60991676;