rs4767461

chr12-116849176-C-T

Variant summary

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

The NM_001382266.1(RNFT2):c.1201-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 611,004 control chromosomes in the GnomAD database, including 139,447 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 0.55 (28828 hom., cov: 30)
  • Exomes 𝑓: 0.68 (110619 hom.)
• Consequence: RNFT2 NM_001382266.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

Genes affected

RNFT2 (HGNC:25905): (ring finger protein, transmembrane 2) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in positive regulation of ERAD pathway and protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNFT2	NM_001382266.1	c.1201-138C>T		intron_variant		ENST00000257575.9
RNFT2	NM_001109903.2	c.1201-138C>T		intron_variant
RNFT2	NM_032814.4	c.1201-3474C>T		intron_variant
RNFT2	XM_047429745.1	c.1201-3162C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNFT2	ENST00000257575.9	c.1201-138C>T		intron_variant		5	NM_001382266.1	P1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84158 AN: 151816 Hom.: 28819 Cov.: 30

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.593

GnomAD4 exome AF: 0.678 AC: 311363 AN: 459068 Hom.: 110619 AF XY: 0.672 AC XY: 160982 AN XY: 239564

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.768

Gnomad4 ASJ exome AF: 0.743

Gnomad4 EAS exome AF: 0.443

Gnomad4 SAS exome AF: 0.498

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.742

Gnomad4 OTH exome AF: 0.654

GnomAD4 genome AF: 0.554 AC: 84170 AN: 151936 Hom.: 28828 Cov.: 30 AF XY: 0.555 AC XY: 41196 AN XY: 74244

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.594

Alfa AF: 0.713 Hom.: 68641

Bravo AF: 0.536

Asia WGS AF: 0.464 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.44
Dann	Benign	0.70

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: rs4767461; hg19: chr12-117286981; COSMIC: COSV57487025;