rs4968401

Positions:

• chr17-59963369-T-C

Variant summary

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

The NM_016125.4(RNFT1):​c.57-85A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,134,166 control chromosomes in the GnomAD database, including 167,177 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 0.44 (16891 hom., cov: 31)
  • Exomes 𝑓: 0.55 (150286 hom.)
• Consequence: RNFT1 NM_016125.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.78

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]

TBC1D3P1-DHX40P1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNFT1	NM_016125.4	c.57-85A>G		intron_variant		ENST00000305783.13	NP_057209.3
TBC1D3P1-DHX40P1	NR_002924.3	n.1207-85A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNFT1	ENST00000305783.13	c.57-85A>G		intron_variant		1	NM_016125.4	ENSP00000304670	P1

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67277 AN: 151816 Hom.: 16893 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.547 AC: 537304 AN: 982232 Hom.: 150286 AF XY: 0.549 AC XY: 272093 AN XY: 495396

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.554

Gnomad4 ASJ exome AF: 0.578

Gnomad4 EAS exome AF: 0.417

Gnomad4 SAS exome AF: 0.572

Gnomad4 FIN exome AF: 0.564

Gnomad4 NFE exome AF: 0.563

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.443 AC: 67281 AN: 151934 Hom.: 16891 Cov.: 31 AF XY: 0.446 AC XY: 33115 AN XY: 74232

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.441

Alfa AF: 0.496 Hom.: 2494

Bravo AF: 0.426

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	12
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4968401; hg19: chr17-58040730; COSMIC: COSV59870010; COSMIC: COSV59870010;