rs2228309

Positions:

• chr17-82093307-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004104.5(FASN):​c.567T>C​(p.Asn189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 1,596,526 control chromosomes in the GnomAD database, including 239,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (20291 hom., cov: 34)
  • Exomes 𝑓: 0.54 (218728 hom.)
• Consequence: FASN NM_004104.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.70

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 17-82093307-A-G is Benign according to our data. Variant chr17-82093307-A-G is described in ClinVar as [Benign]. Clinvar id is 1170035.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82093307-A-G is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5	c.567T>C	p.Asn189=	synonymous_variant	5/43	ENST00000306749.4
FASN	XM_011523538.3	c.567T>C	p.Asn189=	synonymous_variant	5/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4	c.567T>C	p.Asn189=	synonymous_variant	5/43	1	NM_004104.5	P1
FASN	ENST00000634990.1	c.567T>C	p.Asn189=	synonymous_variant	5/43	5

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77245 AN: 152042 Hom.: 20289 Cov.: 34

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.501

GnomAD3 exomes AF: 0.463 AC: 102735 AN: 221732 Hom.: 25640 AF XY: 0.470 AC XY: 56296 AN XY: 119800

Gnomad AFR exome AF: 0.482

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.384

Gnomad EAS exome AF: 0.146

Gnomad SAS exome AF: 0.427

Gnomad FIN exome AF: 0.551

Gnomad NFE exome AF: 0.568

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.542 AC: 782135 AN: 1444366 Hom.: 218728 Cov.: 57 AF XY: 0.538 AC XY: 385474 AN XY: 716888

Gnomad4 AFR exome AF: 0.485

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.430

Gnomad4 FIN exome AF: 0.553

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.504

GnomAD4 genome AF: 0.508 AC: 77265 AN: 152160 Hom.: 20291 Cov.: 34 AF XY: 0.502 AC XY: 37342 AN XY: 74388

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.408

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.419

Gnomad4 FIN AF: 0.543

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.496

Alfa AF: 0.539 Hom.: 10798

Bravo AF: 0.493

Asia WGS AF: 0.288 AC: 1002 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epileptic encephalopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.2
DANN	Benign	0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs2228309; hg19: chr17-80051183; COSMIC: COSV60751005; COSMIC: COSV60751005;