8-11803341-G-A

Position:

• chr8-11803341-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004462.5(FDFT1):​c.99+410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,291,940 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (32 hom.)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.459

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-11803341-G-A is Benign according to our data. Variant chr8-11803341-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2499068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_004462.5	c.99+410G>A		intron_variant		ENST00000220584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000220584.9	c.99+410G>A		intron_variant		1	NM_004462.5	P1

Frequencies

GnomAD3 genomes AF: 0.00599 AC: 911 AN: 152186 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00747

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00471 AC: 605 AN: 128458 Hom.: 8 AF XY: 0.00455 AC XY: 320 AN XY: 70334

Gnomad AFR exome AF: 0.000328

Gnomad AMR exome AF: 0.000780

Gnomad ASJ exome AF: 0.00321

Gnomad EAS exome AF: 0.000192

Gnomad SAS exome AF: 0.00206

Gnomad FIN exome AF: 0.0375

Gnomad NFE exome AF: 0.00587

Gnomad OTH exome AF: 0.00699

GnomAD4 exome AF: 0.00445 AC: 5077 AN: 1139636 Hom.: 32 Cov.: 35 AF XY: 0.00454 AC XY: 2538 AN XY: 559100

Gnomad4 AFR exome AF: 0.000408

Gnomad4 AMR exome AF: 0.000883

Gnomad4 ASJ exome AF: 0.00237

Gnomad4 EAS exome AF: 0.000154

Gnomad4 SAS exome AF: 0.00195

Gnomad4 FIN exome AF: 0.0289

Gnomad4 NFE exome AF: 0.00467

Gnomad4 OTH exome AF: 0.00403

GnomAD4 genome AF: 0.00599 AC: 912 AN: 152304 Hom.: 10 Cov.: 32 AF XY: 0.00697 AC XY: 519 AN XY: 74462

Gnomad4 AFR AF: 0.000698

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.00747

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00845 Hom.: 3

Bravo AF: 0.00298

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

FDFT1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.84

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: rs141381802; hg19: chr8-11660850;