8-11803341-G-A

Variant names:

• chr8-11803341-G-A
• rs141381802
• NM_004462.5:c.99+410G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001287745.2(FDFT1):​c.-271G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00464 in 1,291,940 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (32 hom.)
• Consequence: FDFT1 NM_001287745.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.459
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-11803341-G-A is Benign according to our data. Variant chr8-11803341-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2499068.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287745.2. 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.99+410G>A		intron	N/A	NP_004453.3
	FDFT1	NM_001287745.2		c.-271G>A		5_prime_UTR	Exon 2 of 9	NP_001274674.1	P37268-2
	FDFT1	NM_001287747.2		c.-271G>A		5_prime_UTR	Exon 1 of 8	NP_001274676.1	P37268-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	ENST00000220584.9	TSL:1 MANE Select	c.99+410G>A		intron	N/A	ENSP00000220584.4	P37268-1
	FDFT1	ENST00000527045.1	TSL:1	n.168G>A		non_coding_transcript_exon	Exon 2 of 2
	FDFT1	ENST00000529464.5	TSL:1	n.99+410G>A		intron	N/A	ENSP00000434770.1	E9PNJ2

Frequencies

GnomAD3 genomes AF: 0.00599 AC: 911 AN: 152186 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00747

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00471 AC: 605 AN: 128458 AF XY: 0.00455

Gnomad AFR exome AF: 0.000328

Gnomad AMR exome AF: 0.000780

Gnomad ASJ exome AF: 0.00321

Gnomad EAS exome AF: 0.000192

Gnomad FIN exome AF: 0.0375

Gnomad NFE exome AF: 0.00587

Gnomad OTH exome AF: 0.00699

GnomAD4 exome AF: 0.00445 AC: 5077 AN: 1139636 Hom.: 32 Cov.: 35 AF XY: 0.00454 AC XY: 2538 AN XY: 559100

African (AFR) AF: 0.000408 AC: 10 AN: 24524

American (AMR) AF: 0.000883 AC: 25 AN: 28328

Ashkenazi Jewish (ASJ) AF: 0.00237 AC: 38 AN: 16064

East Asian (EAS) AF: 0.000154 AC: 2 AN: 12980

South Asian (SAS) AF: 0.00195 AC: 149 AN: 76224

European-Finnish (FIN) AF: 0.0289 AC: 369 AN: 12786

Middle Eastern (MID) AF: 0.00159 AC: 7 AN: 4412

European-Non Finnish (NFE) AF: 0.00467 AC: 4309 AN: 922604

Other (OTH) AF: 0.00403 AC: 168 AN: 41714

GnomAD4 genome AF: 0.00599 AC: 912 AN: 152304 Hom.: 10 Cov.: 32 AF XY: 0.00697 AC XY: 519 AN XY: 74462

African (AFR) AF: 0.000698 AC: 29 AN: 41574

American (AMR) AF: 0.000784 AC: 12 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4826

European-Finnish (FIN) AF: 0.0311 AC: 330 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00747 AC: 508 AN: 68028

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00845 Hom.: 3

Bravo AF: 0.00298

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.84
PhyloP100		0.46
PromoterAI		0.0065	Neutral
Mutation Taster		=100/0	polymorphism

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: rs141381802; hg19: chr8-11660850;