chr8-11808709-G-GTCCCACTCCCACTCCCACTCCCACTCCCAC

Position:

• chr8-11808709-G-GTCCCACTCCCACTCCCACTCCCACTCCCAC

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004462.5(FDFT1):​c.100-75_100-46dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00040 (4 hom.)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U: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 -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_004462.5	c.100-75_100-46dup		intron_variant		ENST00000220584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000220584.9	c.100-75_100-46dup		intron_variant		1	NM_004462.5	P1

Frequencies

GnomAD3 genomes AF: 0.000329 AC: 49 AN: 148922 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000398

Gnomad ASJ AF: 0.00145

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00301

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000297

Gnomad OTH AF: 0.00147

GnomAD4 exome AF: 0.000401 AC: 548 AN: 1366048 Hom.: 4 Cov.: 0 AF XY: 0.000513 AC XY: 345 AN XY: 672634

Gnomad4 AFR exome AF: 0.0000318

Gnomad4 AMR exome AF: 0.000569

Gnomad4 ASJ exome AF: 0.000810

Gnomad4 EAS exome AF: 0.000781

Gnomad4 SAS exome AF: 0.00408

Gnomad4 FIN exome AF: 0.0000251

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.000491

GnomAD4 genome AF: 0.000329 AC: 49 AN: 149034 Hom.: 0 Cov.: 0 AF XY: 0.000385 AC XY: 28 AN XY: 72636

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000398

Gnomad4 ASJ AF: 0.00145

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00301

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000297

Gnomad4 OTH AF: 0.00145

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Squalene synthase deficiency Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Mar 19, 2020

- -

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;