rs180511

Variant names:

• chr17-59955087-G-A
• rs180511
• NM_016125.4:c.1072-941C>T

Variant summary

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

The NM_016125.4(RNFT1):​c.1072-941C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,124 control chromosomes in the GnomAD database, including 1,693 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 0.14 (1693 hom., cov: 32)
• Consequence: RNFT1 NM_016125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254
• Publications: 5 publications found

Genes affected

RNFT1 (HGNC:30206): (ring finger protein, transmembrane 1) Enables ubiquitin binding activity and ubiquitin protein ligase activity. Involved in positive regulation of ERAD pathway and protein autoubiquitination. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267318 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNFT1	NM_016125.4	c.1072-941C>T		intron_variant	Intron 7 of 8	ENST00000305783.13	NP_057209.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNFT1	ENST00000305783.13	c.1072-941C>T		intron_variant	Intron 7 of 8	1	NM_016125.4	ENSP00000304670.8
ENSG00000267318	ENST00000591035.1	c.149+9569G>A		intron_variant	Intron 2 of 3	3		ENSP00000468280.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21617 AN: 152006 Hom.: 1694 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.0536

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.142 AC: 21608 AN: 152124 Hom.: 1693 Cov.: 32 AF XY: 0.142 AC XY: 10573 AN XY: 74362

African (AFR) AF: 0.104 AC: 4331 AN: 41502

American (AMR) AF: 0.162 AC: 2475 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3468

East Asian (EAS) AF: 0.0536 AC: 278 AN: 5190

South Asian (SAS) AF: 0.106 AC: 511 AN: 4822

European-Finnish (FIN) AF: 0.158 AC: 1670 AN: 10566

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11143 AN: 67982

Other (OTH) AF: 0.152 AC: 321 AN: 2114

Alfa AF: 0.149 Hom.: 210

Bravo AF: 0.141

Asia WGS AF: 0.0770 AC: 269 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.72
PhyloP100		-0.25
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: rs180511; hg19: chr17-58032448;