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. The variant received -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. 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. 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
• 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 -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 VariationId is 3057202.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0596 is higher than 0.05.

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.100-57_100-46delCACTCCCACTCC		intron	N/A	NP_004453.3
	FDFT1	NM_001287750.2		c.220_231delCACTCCCACTCC	p.His74_Ser77del	conservative_inframe_deletion	Exon 1 of 7	NP_001274679.1	A0A1W2PQ47
	FDFT1	NM_001287742.2		c.100-57_100-46delCACTCCCACTCC		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.100-57_100-46delCACTCCCACTCC		intron	N/A	ENSP00000220584.4	P37268-1
	FDFT1	ENST00000529464.5	TSL:1	n.100-930_100-919delCACTCCCACTCC		intron	N/A	ENSP00000434770.1	E9PNJ2
	FDFT1	ENST00000525954.5	TSL:2	c.220_231delCACTCCCACTCC	p.His74_Ser77del	conservative_inframe_deletion	Exon 1 of 7	ENSP00000491537.1	A0A1W2PQ47

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

African (AFR) AF: 0.0651 AC: 2049 AN: 31476

American (AMR) AF: 0.00849 AC: 298 AN: 35104

Ashkenazi Jewish (ASJ) AF: 0.00733 AC: 172 AN: 23452

East Asian (EAS) AF: 0.00377 AC: 135 AN: 35816

South Asian (SAS) AF: 0.00643 AC: 488 AN: 75894

European-Finnish (FIN) AF: 0.0528 AC: 2102 AN: 39842

Middle Eastern (MID) AF: 0.0113 AC: 63 AN: 5568

European-Non Finnish (NFE) AF: 0.0163 AC: 17340 AN: 1061300

Other (OTH) AF: 0.0164 AC: 936 AN: 57030

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

African (AFR) AF: 0.0616 AC: 2464 AN: 39992

American (AMR) AF: 0.0113 AC: 171 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.00492 AC: 17 AN: 3456

East Asian (EAS) AF: 0.00565 AC: 28 AN: 4952

South Asian (SAS) AF: 0.00473 AC: 22 AN: 4654

European-Finnish (FIN) AF: 0.0584 AC: 601 AN: 10290

Middle Eastern (MID) AF: 0.0138 AC: 4 AN: 290

European-Non Finnish (NFE) AF: 0.0171 AC: 1149 AN: 67314

Other (OTH) AF: 0.0189 AC: 39 AN: 2068

Alfa AF: 0.0232 Hom.: 2006

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FDFT1-related disorder (1)

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;