rs2645430

Positions:

• chr8-11801600-A-G
• chr8-11801600-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000531395.1(ENSG00000255046):​n.591+322T>C variant causes a intron, non coding transcript 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: ENST00000531395.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FDFT1	NM_001287742.2	c.-272-658A>G		intron_variant			NP_001274671.1
FDFT1	NM_001287743.2	c.-74-1159A>G		intron_variant			NP_001274672.1
FDFT1	NM_001287744.2	c.-94+5589A>G		intron_variant			NP_001274673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000531395.1	n.591+322T>C		intron_variant, non_coding_transcript_variant		3
FDFT1	ENST00000615631.4	c.-74-1159A>G		intron_variant		5		ENSP00000481481	P1

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

Gnomad4 AFR exome AF: 0.228

Gnomad4 AMR exome AF: 0.593

Gnomad4 ASJ exome AF: 0.512

Gnomad4 EAS exome AF: 0.659

Gnomad4 SAS exome AF: 0.676

Gnomad4 FIN exome AF: 0.622

Gnomad4 NFE exome AF: 0.586

Gnomad4 OTH exome AF: 0.567

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

Gnomad4 AFR AF: 0.251

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.661

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.507

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs2645430; hg19: chr8-11659109;