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. The variant received -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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 15 publications found

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]

FDFT1 Gene-Disease associations (from GenCC):

• retinitis pigmentosa

  Inheritance: AR Classification: LIMITED Submitted by: G2P
• squalene synthase deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287750.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	NM_004462.5	MANE Select	c.100-63_100-46delCACTCCCACTCCCACTCC		intron	N/A	NP_004453.3
	FDFT1	NM_001287750.2		c.214_231delCACTCCCACTCCCACTCC	p.His72_Ser77del	conservative_inframe_deletion	Exon 1 of 7	NP_001274679.1	A0A1W2PQ47
	FDFT1	NM_001287742.2		c.100-63_100-46delCACTCCCACTCCCACTCC		intron	N/A	NP_001274671.1	Q6IAX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	ENST00000220584.9	TSL:1 MANE Select	c.100-63_100-46delCACTCCCACTCCCACTCC		intron	N/A	ENSP00000220584.4	P37268-1
	FDFT1	ENST00000529464.5	TSL:1	n.100-936_100-919delCACTCCCACTCCCACTCC		intron	N/A	ENSP00000434770.1	E9PNJ2
	FDFT1	ENST00000525954.5	TSL:2	c.214_231delCACTCCCACTCCCACTCC	p.His72_Ser77del	conservative_inframe_deletion	Exon 1 of 7	ENSP00000491537.1	A0A1W2PQ47

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

African (AFR) AF: 0.0228 AC: 717 AN: 31490

American (AMR) AF: 0.00213 AC: 75 AN: 35136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23468

East Asian (EAS) AF: 0.000447 AC: 16 AN: 35834

South Asian (SAS) AF: 0.000250 AC: 19 AN: 75938

European-Finnish (FIN) AF: 0.0000753 AC: 3 AN: 39866

Middle Eastern (MID) AF: 0.000718 AC: 4 AN: 5568

European-Non Finnish (NFE) AF: 0.000351 AC: 373 AN: 1061692

Other (OTH) AF: 0.00177 AC: 101 AN: 57050

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

African (AFR) AF: 0.0227 AC: 907 AN: 40004

American (AMR) AF: 0.00292 AC: 44 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3456

East Asian (EAS) AF: 0.00121 AC: 6 AN: 4952

South Asian (SAS) AF: 0.00 AC: 0 AN: 4654

European-Finnish (FIN) AF: 0.000194 AC: 2 AN: 10296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000401 AC: 27 AN: 67320

Other (OTH) AF: 0.00532 AC: 11 AN: 2068

Alfa AF: 0.00 Hom.: 2006

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs71711801; hg19: chr8-11666218;