chr8-11813532-G-A

Variant names:

• chr8-11813532-G-A
• rs1736058
• NM_004462.5:c.381+3682G>A

Variant summary

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

The NM_004462.5(FDFT1):​c.381+3682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,096 control chromosomes in the GnomAD database, including 2,935 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 0.18 (2935 hom., cov: 32)
• Consequence: FDFT1 NM_004462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.96
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004462.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	NM_004462.5	MANE Select	c.381+3682G>A		intron	N/A	NP_004453.3
	FDFT1	NM_001287750.2		c.558+3682G>A		intron	N/A	NP_001274679.1
	FDFT1	NM_001287742.2		c.381+3682G>A		intron	N/A	NP_001274671.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	ENST00000220584.9	TSL:1 MANE Select	c.381+3682G>A		intron	N/A	ENSP00000220584.4
	FDFT1	ENST00000529464.5	TSL:1	n.*127+3682G>A		intron	N/A	ENSP00000434770.1
	FDFT1	ENST00000525954.5	TSL:2	c.558+3682G>A		intron	N/A	ENSP00000491537.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27753 AN: 151980 Hom.: 2938 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.186

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.183 AC: 27773 AN: 152096 Hom.: 2935 Cov.: 32 AF XY: 0.189 AC XY: 14034 AN XY: 74346

African (AFR) AF: 0.112 AC: 4645 AN: 41492

American (AMR) AF: 0.211 AC: 3233 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 420 AN: 3472

East Asian (EAS) AF: 0.429 AC: 2216 AN: 5162

South Asian (SAS) AF: 0.264 AC: 1273 AN: 4818

European-Finnish (FIN) AF: 0.234 AC: 2474 AN: 10568

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12880 AN: 67982

Other (OTH) AF: 0.188 AC: 398 AN: 2112

Alfa AF: 0.192 Hom.: 13486

Bravo AF: 0.179

Asia WGS AF: 0.331 AC: 1147 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.63
DANN	Benign	0.51
PhyloP100		-3.0
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: rs1736058; hg19: chr8-11671041;