8-11801600-A-G

Variant names:

• chr8-11801600-A-G
• rs2645430
• NM_001287742.2:c.-272-658A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001287742.2(FDFT1):​c.-272-658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 190,460 control chromosomes in the GnomAD database, including 27,940 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (20601 hom., cov: 33)
  • Exomes 𝑓: 0.61 (7339 hom.)
• Consequence: FDFT1 NM_001287742.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832
• Publications: 17 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

ENSG00000255046 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287742.2. 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_001287742.2		c.-272-658A>G		intron	N/A	NP_001274671.1	Q6IAX1
	FDFT1	NM_001287743.2		c.-74-1159A>G		intron	N/A	NP_001274672.1	P37268-1
	FDFT1	NM_001287744.2		c.-94+5589A>G		intron	N/A	NP_001274673.1	P37268-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	ENST00000615631.5	TSL:5	c.-74-1159A>G		intron	N/A	ENSP00000481481.1	P37268-1
	FDFT1	ENST00000866105.1		c.-272-658A>G		intron	N/A	ENSP00000536164.1
	FDFT1	ENST00000866106.1		c.-273+154A>G		intron	N/A	ENSP00000536165.1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75475 AN: 151048 Hom.: 20590 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.605 AC: 23794 AN: 39304 Hom.: 7339 AF XY: 0.612 AC XY: 13669 AN XY: 22334

African (AFR) AF: 0.228 AC: 42 AN: 184

American (AMR) AF: 0.593 AC: 1974 AN: 3330

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 291 AN: 568

East Asian (EAS) AF: 0.659 AC: 535 AN: 812

South Asian (SAS) AF: 0.676 AC: 5999 AN: 8880

European-Finnish (FIN) AF: 0.622 AC: 638 AN: 1026

Middle Eastern (MID) AF: 0.472 AC: 51 AN: 108

European-Non Finnish (NFE) AF: 0.586 AC: 13239 AN: 22588

Other (OTH) AF: 0.567 AC: 1025 AN: 1808

GnomAD4 genome AF: 0.499 AC: 75502 AN: 151156 Hom.: 20601 Cov.: 33 AF XY: 0.508 AC XY: 37532 AN XY: 73896

African (AFR) AF: 0.251 AC: 10284 AN: 40944

American (AMR) AF: 0.569 AC: 8676 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1746 AN: 3462

East Asian (EAS) AF: 0.670 AC: 3410 AN: 5092

South Asian (SAS) AF: 0.676 AC: 3264 AN: 4828

European-Finnish (FIN) AF: 0.661 AC: 6959 AN: 10528

Middle Eastern (MID) AF: 0.472 AC: 135 AN: 286

European-Non Finnish (NFE) AF: 0.581 AC: 39391 AN: 67782

Other (OTH) AF: 0.507 AC: 1064 AN: 2100

Alfa AF: 0.420 Hom.: 1335

Bravo AF: 0.478

Asia WGS AF: 0.668 AC: 2324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.14
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2645430; hg19: chr8-11659109;