rs34179714

chr17-82087171-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004104.5(FASN):c.3306C>G(p.Ala1102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,609,482 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (8 hom., cov: 33)
  • Exomes 𝑓: 0.0065 (76 hom.)
• Consequence: FASN NM_004104.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.300

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 Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 17-82087171-G-C is Benign according to our data. Variant chr17-82087171-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 462033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-82087171-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.3 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00653 (9516/1457218) while in subpopulation MID AF= 0.0233 (133/5716). AF 95% confidence interval is 0.0201. There are 76 homozygotes in gnomad4_exome. There are 4822 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 848 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5	c.3306C>G	p.Ala1102=	synonymous_variant	21/43	ENST00000306749.4
FASN	XM_011523538.3	c.3306C>G	p.Ala1102=	synonymous_variant	21/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4	c.3306C>G	p.Ala1102=	synonymous_variant	21/43	1	NM_004104.5	P1
FASN	ENST00000634990.1	c.3306C>G	p.Ala1102=	synonymous_variant	21/43	5

Frequencies

GnomAD3 genomes AF: 0.00557 AC: 848 AN: 152146 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00104

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00681

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00713 AC: 1703 AN: 238752 Hom.: 18 AF XY: 0.00732 AC XY: 952 AN XY: 130002

Gnomad AFR exome AF: 0.00127

Gnomad AMR exome AF: 0.00378

Gnomad ASJ exome AF: 0.0458

Gnomad EAS exome AF: 0.000112

Gnomad SAS exome AF: 0.00465

Gnomad FIN exome AF: 0.00247

Gnomad NFE exome AF: 0.00812

Gnomad OTH exome AF: 0.00935

GnomAD4 exome AF: 0.00653 AC: 9516 AN: 1457218 Hom.: 76 Cov.: 33 AF XY: 0.00665 AC XY: 4822 AN XY: 724646

Gnomad4 AFR exome AF: 0.00176

Gnomad4 AMR exome AF: 0.00400

Gnomad4 ASJ exome AF: 0.0481

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00442

Gnomad4 FIN exome AF: 0.00416

Gnomad4 NFE exome AF: 0.00607

Gnomad4 OTH exome AF: 0.00918

GnomAD4 genome AF: 0.00556 AC: 847 AN: 152264 Hom.: 8 Cov.: 33 AF XY: 0.00543 AC XY: 404 AN XY: 74456

Gnomad4 AFR AF: 0.00103

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.0458

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00539

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.00682

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0111 Hom.: 5

Bravo AF: 0.00585

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Epileptic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

FASN: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	4.8
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs34179714; hg19: chr17-80045047; COSMIC: COSV60754878; COSMIC: COSV60754878;