8-11838843-T-G

Variant names:

• chr8-11838843-T-G
• rs3258
• NM_004462.5:c.*234T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000220584.9(FDFT1):​c.*234T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 382,956 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000026 (0 hom.)
• Consequence: FDFT1 ENST00000220584.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000220584.9. 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.*234T>G		3_prime_UTR	Exon 8 of 8	NP_004453.3
	FDFT1	NM_001287750.2		c.*234T>G		3_prime_UTR	Exon 7 of 7	NP_001274679.1
	FDFT1	NM_001287742.2		c.*234T>G		3_prime_UTR	Exon 10 of 10	NP_001274671.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FDFT1	ENST00000220584.9	TSL:1 MANE Select	c.*234T>G		3_prime_UTR	Exon 8 of 8	ENSP00000220584.4
	FDFT1	ENST00000446331.6	TSL:2	n.1191T>G		non_coding_transcript_exon	Exon 5 of 5
	FDFT1	ENST00000525954.5	TSL:2	c.*234T>G		3_prime_UTR	Exon 7 of 7	ENSP00000491537.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000261 AC: 1 AN: 382956 Hom.: 0 Cov.: 2 AF XY: 0.00000490 AC XY: 1 AN XY: 203956

African (AFR) AF: 0.00 AC: 0 AN: 10974

American (AMR) AF: 0.00 AC: 0 AN: 15364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11744

East Asian (EAS) AF: 0.00 AC: 0 AN: 24856

South Asian (SAS) AF: 0.0000226 AC: 1 AN: 44300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1628

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 229754

Other (OTH) AF: 0.00 AC: 0 AN: 21954

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		-0.38

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: rs3258; hg19: chr8-11696352;