8-11808709-GTCCCACTCCCAC-G

Variant names:

• chr8-11808709-GTCCCACTCCCAC-G
• rs71711801
• NM_004462.5:c.100-57_100-46delCACTCCCACTCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP3 BP6 BA1

The NM_001287750.2(FDFT1):​c.220_231delCACTCCCACTCC​(p.His74_Ser77del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,514,486 control chromosomes in the GnomAD database, including 394 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.030 (104 hom., cov: 0)
  • Exomes 𝑓: 0.017 (290 hom.)
• Consequence: FDFT1 NM_001287750.2 conservative_inframe_deletion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.40

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.

• BP3: Nonframeshift variant in repetitive region in NM_001287750.2
• BP6: Variant 8-11808709-GTCCCACTCCCAC-G is Benign according to our data. Variant chr8-11808709-GTCCCACTCCCAC-G is described in ClinVar as [Benign]. Clinvar id is 3057202.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-11808709-GTCCCACTCCCAC-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.100-57_100-46delCACTCCCACTCC		intron_variant	Intron 1 of 7	ENST00000220584.9	NP_004453.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FDFT1	ENST00000220584.9	c.100-57_100-46delCACTCCCACTCC		intron_variant	Intron 1 of 7	1	NM_004462.5	ENSP00000220584.4

Frequencies

GnomAD3 genomes AF: 0.0300 AC: 4473 AN: 148892 Hom.: 101 Cov.: 0

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0114

Gnomad ASJ AF: 0.00492

Gnomad EAS AF: 0.00564

Gnomad SAS AF: 0.00494

Gnomad FIN AF: 0.0584

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0191

GnomAD4 exome AF: 0.0173 AC: 23583 AN: 1365482 Hom.: 290 AF XY: 0.0169 AC XY: 11352 AN XY: 672368

Gnomad4 AFR exome AF: 0.0651

Gnomad4 AMR exome AF: 0.00849

Gnomad4 ASJ exome AF: 0.00733

Gnomad4 EAS exome AF: 0.00377

Gnomad4 SAS exome AF: 0.00643

Gnomad4 FIN exome AF: 0.0528

Gnomad4 NFE exome AF: 0.0163

Gnomad4 OTH exome AF: 0.0164

GnomAD4 genome AF: 0.0302 AC: 4496 AN: 149004 Hom.: 104 Cov.: 0 AF XY: 0.0316 AC XY: 2297 AN XY: 72618

Gnomad4 AFR AF: 0.0616

Gnomad4 AMR AF: 0.0113

Gnomad4 ASJ AF: 0.00492

Gnomad4 EAS AF: 0.00565

Gnomad4 SAS AF: 0.00473

Gnomad4 FIN AF: 0.0584

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0189

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

FDFT1-related disorder Benign:1

Dec 05, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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;