Variant 8-11808615-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004462.5(FDFT1):c.100-179C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,390,718 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 20 hom. )

Consequence

FDFT1
NM_004462.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.286

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041832626).

BP6

Variant 8-11808615-C-G is Benign according to our data. Variant chr8-11808615-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2571307.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FDFT1	NM_004462.5 linkuse as main transcript	c.100-179C>G		intron_variant		ENST00000220584.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FDFT1	ENST00000220584.9 linkuse as main transcript	c.100-179C>G		intron_variant		1	NM_004462.5	P1	P37268-1

Frequencies

GnomAD3 genomes

AF:

0.00274

AC:

417

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00421

Gnomad OTH

AF:

0.00288

GnomAD4 exome

AF:

0.00475

AC:

5885

AN:

1238586

Hom.:

Cov.:

AF XY:

0.00482

AC XY:

2891

AN XY:

599560

show subpopulations

Gnomad4 AFR exome

AF:

0.000700

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00231

Gnomad4 FIN exome

AF:

0.00205

Gnomad4 NFE exome

AF:

0.00515

Gnomad4 OTH exome

AF:

0.00411

GnomAD4 genome

AF:

0.00274

AC:

417

AN:

152132

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

179

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000530

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00421

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.000479

Hom.:

Bravo

AF:

0.00284

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00545

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

FDFT1: BS2 -

FDFT1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.80

FATHMM_MKL

Benign

0.048

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0042

MutationTaster

Benign

1.0

N;N;N;N;N;N

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

gMVP

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over