8-11808709-GTCCCACTCCCACTCCCACTCCCACTCCCAC-GTCCCACTCCCAC

Variant names:

• chr8-11808709-GTCCCACTCCCACTCCCAC-G
• rs71711801
• NM_004462.5:c.100-63_100-46delCACTCCCACTCCCACTCC

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_001287750.2(FDFT1):​c.214_231delCACTCCCACTCCCACTCC​(p.His72_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 0.00152 in 1,515,070 control chromosomes in the GnomAD database, including 17 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0067 (9 hom., cov: 0)
  • Exomes 𝑓: 0.00096 (8 hom.)
• Consequence: FDFT1 NM_001287750.2 conservative_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• 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 -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001287750.2
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0067 (998/149028) while in subpopulation AFR AF= 0.0227 (907/40004). AF 95% confidence interval is 0.0214. There are 9 homozygotes in gnomad4. There are 490 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FDFT1	NM_004462.5	c.100-63_100-46delCACTCCCACTCCCACTCC		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.100-63_100-46delCACTCCCACTCCCACTCC		intron_variant	Intron 1 of 7	1	NM_004462.5	ENSP00000220584.4

Frequencies

GnomAD3 genomes AF: 0.00668 AC: 995 AN: 148916 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.0227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00292

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00101

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000194

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000401

Gnomad OTH AF: 0.00538

GnomAD4 exome AF: 0.000958 AC: 1308 AN: 1366042 Hom.: 8 AF XY: 0.000849 AC XY: 571 AN XY: 672634

Gnomad4 AFR exome AF: 0.0228

Gnomad4 AMR exome AF: 0.00213

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000447

Gnomad4 SAS exome AF: 0.000250

Gnomad4 FIN exome AF: 0.0000753

Gnomad4 NFE exome AF: 0.000351

Gnomad4 OTH exome AF: 0.00177

GnomAD4 genome AF: 0.00670 AC: 998 AN: 149028 Hom.: 9 Cov.: 0 AF XY: 0.00675 AC XY: 490 AN XY: 72634

Gnomad4 AFR AF: 0.0227

Gnomad4 AMR AF: 0.00292

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00121

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000194

Gnomad4 NFE AF: 0.000401

Gnomad4 OTH AF: 0.00532

ClinVar

Not reported in ClinVar

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;