rs3258

chr8-11838843-T-C

Variant summary

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

The NM_004462.5(FDFT1):c.*234T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 534,182 control chromosomes in the GnomAD database, including 40,348 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 0.39 (11579 hom., cov: 32)
  • Exomes 𝑓: 0.38 (28769 hom.)
• Consequence: FDFT1 NM_004462.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

Genes affected

FDFT1 (HGNC:3629): (farnesyl-diphosphate farnesyltransferase 1) This gene encodes a membrane-associated enzyme located at a branch point in the mevalonate pathway. The encoded protein is the first specific enzyme in cholesterol biosynthesis, catalyzing the dimerization of two molecules of farnesyl diphosphate in a two-step reaction to form squalene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_004462.5	c.*234T>C		3_prime_UTR_variant	8/8	ENST00000220584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000220584.9	c.*234T>C		3_prime_UTR_variant	8/8	1	NM_004462.5	P1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58864 AN: 151966 Hom.: 11582 Cov.: 32

Gnomad AFR AF: 0.386

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.383 AC: 146392 AN: 382098 Hom.: 28769 Cov.: 2 AF XY: 0.385 AC XY: 78414 AN XY: 203526

Gnomad4 AFR exome AF: 0.378

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.374

Gnomad4 EAS exome AF: 0.520

Gnomad4 SAS exome AF: 0.431

Gnomad4 FIN exome AF: 0.468

Gnomad4 NFE exome AF: 0.346

Gnomad4 OTH exome AF: 0.366

GnomAD4 genome AF: 0.387 AC: 58883 AN: 152084 Hom.: 11579 Cov.: 32 AF XY: 0.394 AC XY: 29296 AN XY: 74332

Gnomad4 AFR AF: 0.386

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.476

Gnomad4 NFE AF: 0.349

Gnomad4 OTH AF: 0.369

Alfa AF: 0.352 Hom.: 16265

Bravo AF: 0.387

Asia WGS AF: 0.448 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.9
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3258; hg19: chr8-11696352; COSMIC: COSV55042415; COSMIC: COSV55042415;