chr8-11808709-GTCCCAC-G

Variant names:

• chr8-11808709-GTCCCAC-G
• rs71711801
• NM_004462.5:c.100-51_100-46delCACTCC

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP3 BP6_Moderate BA1

The NM_001287750.2(FDFT1):​c.226_231delCACTCC​(p.His76_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 0.933 in 1,514,496 control chromosomes in the GnomAD database, including 660,457 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.89 (58797 hom., cov: 0)
  • Exomes 𝑓: 0.94 (601660 hom.)
• Consequence: FDFT1 NM_001287750.2 conservative_inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:2
• 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 -11 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001287750.2
• BP6: Variant 8-11808709-GTCCCAC-G is Benign according to our data. Variant chr8-11808709-GTCCCAC-G is described in ClinVar as Benign. ClinVar VariationId is 3060113.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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.100-51_100-46delCACTCC		intron	N/A	NP_004453.3
	FDFT1	NM_001287750.2		c.226_231delCACTCC	p.His76_Ser77del	conservative_inframe_deletion	Exon 1 of 7	NP_001274679.1	A0A1W2PQ47
	FDFT1	NM_001287742.2		c.100-51_100-46delCACTCC		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.100-51_100-46delCACTCC		intron	N/A	ENSP00000220584.4	P37268-1
	FDFT1	ENST00000529464.5	TSL:1	n.100-924_100-919delCACTCC		intron	N/A	ENSP00000434770.1	E9PNJ2
	FDFT1	ENST00000525954.5	TSL:2	c.226_231delCACTCC	p.His76_Ser77del	conservative_inframe_deletion	Exon 1 of 7	ENSP00000491537.1	A0A1W2PQ47

Frequencies

GnomAD3 genomes AF: 0.887 AC: 131994 AN: 148834 Hom.: 58785 Cov.: 0

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.975

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.926

Gnomad NFE AF: 0.944

Gnomad OTH AF: 0.898

GnomAD4 exome AF: 0.938 AC: 1280896 AN: 1365550 Hom.: 601660 AF XY: 0.939 AC XY: 631346 AN XY: 672392

African (AFR) AF: 0.741 AC: 23311 AN: 31440

American (AMR) AF: 0.856 AC: 30064 AN: 35108

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 21788 AN: 23460

East Asian (EAS) AF: 0.961 AC: 34423 AN: 35828

South Asian (SAS) AF: 0.947 AC: 71876 AN: 75890

European-Finnish (FIN) AF: 0.912 AC: 36354 AN: 39842

Middle Eastern (MID) AF: 0.903 AC: 5023 AN: 5562

European-Non Finnish (NFE) AF: 0.947 AC: 1005184 AN: 1061392

Other (OTH) AF: 0.927 AC: 52873 AN: 57028

GnomAD4 genome AF: 0.887 AC: 132045 AN: 148946 Hom.: 58797 Cov.: 0 AF XY: 0.885 AC XY: 64258 AN XY: 72586

African (AFR) AF: 0.762 AC: 30455 AN: 39952

American (AMR) AF: 0.886 AC: 13362 AN: 15076

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3199 AN: 3454

East Asian (EAS) AF: 0.965 AC: 4778 AN: 4950

South Asian (SAS) AF: 0.948 AC: 4410 AN: 4654

European-Finnish (FIN) AF: 0.900 AC: 9260 AN: 10288

Middle Eastern (MID) AF: 0.924 AC: 268 AN: 290

European-Non Finnish (NFE) AF: 0.944 AC: 63571 AN: 67308

Other (OTH) AF: 0.899 AC: 1859 AN: 2068

Alfa AF: 0.944 Hom.: 2006

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	FDFT1-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=99/1	polymorphism (auto)

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; COSMIC: COSV105016026; COSMIC: COSV105016026;