rs145542725

chr17-82083107-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004104.5(FASN):c.5574G>A(p.Ala1858=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,610,352 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00017 (1 hom.)
• Consequence: FASN NM_004104.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.484

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 17-82083107-C-T is Benign according to our data. Variant chr17-82083107-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 531093.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82083107-C-T is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5	c.5574G>A	p.Ala1858=	synonymous_variant	33/43	ENST00000306749.4
FASN	XM_011523538.3	c.5574G>A	p.Ala1858=	synonymous_variant	33/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4	c.5574G>A	p.Ala1858=	synonymous_variant	33/43	1	NM_004104.5	P1
FASN	ENST00000634990.1	c.5568G>A	p.Ala1856=	synonymous_variant	33/43	5

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000174 AC: 43 AN: 247184 Hom.: 0 AF XY: 0.000178 AC XY: 24 AN XY: 134490

Gnomad AFR exome AF: 0.0000625

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000116

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000172 AC: 251 AN: 1458040 Hom.: 1 Cov.: 36 AF XY: 0.000170 AC XY: 123 AN XY: 725506

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000514

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000394

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000162

Gnomad4 OTH exome AF: 0.000166

GnomAD4 genome AF: 0.000144 AC: 22 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74480

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000165 Hom.: 0

Bravo AF: 0.000268

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epileptic encephalopathy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Nov 27, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	6.2
Dann	Benign	0.76
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.30		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.30		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs145542725; hg19: chr17-80040983;