17-82093250-G-T

Variant names:

• chr17-82093250-G-T
• rs45624241
• NM_004104.5:c.624C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004104.5(FASN):​c.624C>A​(p.Pro208Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,439,210 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. Synonymous variant affecting the same amino acid position (i.e. P208P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FASN NM_004104.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.89
• Publications: 1 publications found

Genes affected

FASN (HGNC:3594): (fatty acid synthase) The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. In some cancer cell lines, this protein has been found to be fused with estrogen receptor-alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. [provided by RefSeq, Jul 2008]

FASN Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP7: Synonymous conserved (PhyloP=-3.89 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5	c.624C>A	p.Pro208Pro	synonymous_variant	Exon 5 of 43	ENST00000306749.4	NP_004095.4
FASN	XM_011523538.3	c.624C>A	p.Pro208Pro	synonymous_variant	Exon 5 of 43		XP_011521840.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4	c.624C>A	p.Pro208Pro	synonymous_variant	Exon 5 of 43	1	NM_004104.5	ENSP00000304592.2
FASN	ENST00000634990.1	c.624C>A	p.Pro208Pro	synonymous_variant	Exon 5 of 43	5		ENSP00000488964.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1439210 Hom.: 0 Cov.: 34 AF XY: 0.00000140 AC XY: 1 AN XY: 713986

African (AFR) AF: 0.0000603 AC: 2 AN: 33180

American (AMR) AF: 0.00 AC: 0 AN: 41490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25696

East Asian (EAS) AF: 0.00 AC: 0 AN: 38750

South Asian (SAS) AF: 0.00 AC: 0 AN: 82976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50426

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5236

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101922

Other (OTH) AF: 0.00 AC: 0 AN: 59534

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 6

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.096
DANN	Benign	0.85
PhyloP100		-3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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: rs45624241; hg19: chr17-80051126;