chr8-11808709-G-GTCCCACTCCCACTCCCACTCCCAC

Position:

• chr8-11808709-G-GTCCCACTCCCACTCCCACTCCCAC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004462.5(FDFT1):​c.100-69_100-46dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0017 (9 hom.)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.258

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 8-11808709-G-GTCCCACTCCCACTCCCACTCCCAC is Benign according to our data. Variant chr8-11808709-G-GTCCCACTCCCACTCCCACTCCCAC is described in ClinVar as [Likely_benign]. Clinvar id is 3051193.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_004462.5	c.100-69_100-46dup		intron_variant		ENST00000220584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000220584.9	c.100-69_100-46dup		intron_variant		1	NM_004462.5	P1

Frequencies

GnomAD3 genomes AF: 0.00167 AC: 248 AN: 148920 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000326

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000797

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000201

Gnomad SAS AF: 0.0127

Gnomad FIN AF: 0.00340

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.00184

Gnomad OTH AF: 0.00147

GnomAD4 exome AF: 0.00170 AC: 2317 AN: 1366046 Hom.: 9 Cov.: 0 AF XY: 0.00198 AC XY: 1330 AN XY: 672636

Gnomad4 AFR exome AF: 0.000127

Gnomad4 AMR exome AF: 0.000655

Gnomad4 ASJ exome AF: 0.000298

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.00745

Gnomad4 FIN exome AF: 0.00329

Gnomad4 NFE exome AF: 0.00140

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00167 AC: 249 AN: 149032 Hom.: 0 Cov.: 0 AF XY: 0.00189 AC XY: 137 AN XY: 72634

Gnomad4 AFR AF: 0.000350

Gnomad4 AMR AF: 0.000796

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000202

Gnomad4 SAS AF: 0.0127

Gnomad4 FIN AF: 0.00340

Gnomad4 NFE AF: 0.00184

Gnomad4 OTH AF: 0.00145

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

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

Apr 01, 2024

FDFT1: BS1 -

FDFT1-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71711801; hg19: chr8-11666218;