rs4767461

Variant names:

• chr12-116849176-C-T
• rs4767461
• NM_001382266.1:c.1201-138C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382266.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNFT2	NM_001382266.1	MANE Select	c.1201-138C>T		intron	N/A	NP_001369195.1	Q96EX2-1
	RNFT2	NM_001109903.2		c.1201-138C>T		intron	N/A	NP_001103373.1	Q96EX2-1
	RNFT2	NM_032814.4		c.1201-3474C>T		intron	N/A	NP_116203.2	Q96EX2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNFT2	ENST00000257575.9	TSL:5 MANE Select	c.1201-138C>T		intron	N/A	ENSP00000257575.4	Q96EX2-1
	RNFT2	ENST00000392549.7	TSL:5	c.1201-138C>T		intron	N/A	ENSP00000376332.2	Q96EX2-1
	RNFT2	ENST00000407967.7	TSL:5	c.1201-3474C>T		intron	N/A	ENSP00000385669.3	Q96EX2-5

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

African (AFR) AF: 0.137 AC: 1775 AN: 12958

American (AMR) AF: 0.768 AC: 15978 AN: 20816

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 9979 AN: 13432

East Asian (EAS) AF: 0.443 AC: 13535 AN: 30576

South Asian (SAS) AF: 0.498 AC: 21513 AN: 43220

European-Finnish (FIN) AF: 0.762 AC: 22428 AN: 29430

Middle Eastern (MID) AF: 0.557 AC: 1690 AN: 3034

European-Non Finnish (NFE) AF: 0.742 AC: 207627 AN: 279862

Other (OTH) AF: 0.654 AC: 16838 AN: 25740

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

African (AFR) AF: 0.138 AC: 5712 AN: 41468

American (AMR) AF: 0.712 AC: 10872 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.739 AC: 2567 AN: 3472

East Asian (EAS) AF: 0.450 AC: 2319 AN: 5150

South Asian (SAS) AF: 0.500 AC: 2402 AN: 4800

European-Finnish (FIN) AF: 0.749 AC: 7898 AN: 10540

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.741 AC: 50367 AN: 67930

Other (OTH) AF: 0.594 AC: 1252 AN: 2108

Alfa AF: 0.674 Hom.: 102040

Bravo AF: 0.536

Asia WGS AF: 0.464 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.70
PhyloP100		-1.5
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: rs4767461; hg19: chr12-117286981; COSMIC: COSV57487025;