rs1736070

Variant names:

• chr8-11808296-C-T
• rs1736070
• NM_004462.5:c.100-498C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001287749.2(FDFT1):​c.-115C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 1,223,746 control chromosomes in the GnomAD database, including 259,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.58 (26997 hom., cov: 31)
  • Exomes 𝑓: 0.66 (232940 hom.)
• Consequence: FDFT1 NM_001287749.2 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.32
• Publications: 7 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 8-11808296-C-T is Benign according to our data. Variant chr8-11808296-C-T is described in ClinVar as Benign. ClinVar VariationId is 3054358.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287749.2. 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.100-498C>T		intron	N/A	NP_004453.3
	FDFT1	NM_001287749.2		c.-115C>T		5_prime_UTR	Exon 1 of 8	NP_001274678.1	P37268-2
	FDFT1	NM_001287742.2		c.100-498C>T		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.100-498C>T		intron	N/A	ENSP00000220584.4	P37268-1
	FDFT1	ENST00000529464.5	TSL:1	n.100-1371C>T		intron	N/A	ENSP00000434770.1	E9PNJ2
	FDFT1	ENST00000530664.5	TSL:2	c.-115C>T		5_prime_UTR	Exon 1 of 8	ENSP00000432331.1	P37268-2

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88199 AN: 151760 Hom.: 26964 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.657 AC: 704153 AN: 1071868 Hom.: 232940 Cov.: 39 AF XY: 0.656 AC XY: 331916 AN XY: 506062

African (AFR) AF: 0.347 AC: 7854 AN: 22622

American (AMR) AF: 0.680 AC: 5512 AN: 8108

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 7812 AN: 14036

East Asian (EAS) AF: 0.708 AC: 18431 AN: 26036

South Asian (SAS) AF: 0.695 AC: 13118 AN: 18884

European-Finnish (FIN) AF: 0.671 AC: 13892 AN: 20704

Middle Eastern (MID) AF: 0.547 AC: 1573 AN: 2878

European-Non Finnish (NFE) AF: 0.665 AC: 608577 AN: 915442

Other (OTH) AF: 0.635 AC: 27384 AN: 43158

GnomAD4 genome AF: 0.581 AC: 88277 AN: 151878 Hom.: 26997 Cov.: 31 AF XY: 0.587 AC XY: 43538 AN XY: 74232

African (AFR) AF: 0.365 AC: 15129 AN: 41446

American (AMR) AF: 0.667 AC: 10184 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1912 AN: 3470

East Asian (EAS) AF: 0.673 AC: 3446 AN: 5118

South Asian (SAS) AF: 0.719 AC: 3463 AN: 4816

European-Finnish (FIN) AF: 0.688 AC: 7277 AN: 10572

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44851 AN: 67870

Other (OTH) AF: 0.594 AC: 1251 AN: 2106

Alfa AF: 0.606 Hom.: 3626

Bravo AF: 0.570

Asia WGS AF: 0.701 AC: 2441 AN: 3478

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
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.1
DANN	Benign	0.92
PhyloP100		-1.3
PromoterAI		-0.065	Neutral
Mutation Taster		=295/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1736070; hg19: chr8-11665805;