rs1555666767

Variant names:

• chr17-82084006-G-A
• rs1555666767
• NM_004104.5:c.5067C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004104.5(FASN):​c.5067C>T​(p.Leu1689Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,386,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FASN NM_004104.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.177
• Publications: 0 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 17-82084006-G-A is Benign according to our data. Variant chr17-82084006-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 531137.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.177 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004104.5. 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
	FASN	NM_004104.5	MANE Select	c.5067C>T	p.Leu1689Leu	synonymous	Exon 29 of 43	NP_004095.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	ENST00000306749.4	TSL:1 MANE Select	c.5067C>T	p.Leu1689Leu	synonymous	Exon 29 of 43	ENSP00000304592.2	P49327
	FASN	ENST00000940344.1		c.5094C>T	p.Leu1698Leu	synonymous	Exon 29 of 43	ENSP00000610403.1
	FASN	ENST00000940346.1		c.5091C>T	p.Leu1697Leu	synonymous	Exon 29 of 43	ENSP00000610405.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1386840 Hom.: 0 Cov.: 42 AF XY: 0.00000146 AC XY: 1 AN XY: 683922

African (AFR) AF: 0.00 AC: 0 AN: 31488

American (AMR) AF: 0.00 AC: 0 AN: 35556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25072

East Asian (EAS) AF: 0.00 AC: 0 AN: 35650

South Asian (SAS) AF: 0.00 AC: 0 AN: 79096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077398

Other (OTH) AF: 0.00 AC: 0 AN: 57776

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	8.0
DANN	Benign	0.94
PhyloP100		0.18
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: rs1555666767; hg19: chr17-80041882; COSMIC: COSV106452268; COSMIC: COSV106452268;