Variant rs143566258 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004104.5(FASN):c.4617G>C(p.Gly1539=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,588,948 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0062 ( 11 hom., cov: 34)

Exomes 𝑓: 0.00064 ( 6 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 17-82084664-C-G is Benign according to our data. Variant chr17-82084664-C-G is described in ClinVar as [Benign]. Clinvar id is 462060.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.36 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00619 (943/152340) while in subpopulation AFR AF= 0.0217 (902/41584). AF 95% confidence interval is 0.0205. There are 11 homozygotes in gnomad4. There are 436 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 943 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.4617G>C	p.Gly1539=	synonymous_variant	27/43	ENST00000306749.4
FASN	XM_011523538.3 linkuse as main transcript	c.4617G>C	p.Gly1539=	synonymous_variant	27/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.4617G>C	p.Gly1539=	synonymous_variant	27/43	1	NM_004104.5	P1
FASN	ENST00000634990.1 linkuse as main transcript	c.4611G>C	p.Gly1537=	synonymous_variant	27/43	5

Frequencies

GnomAD3 genomes

AF:

0.00620

AC:

944

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00156

AC:

318

AN:

204482

Hom.:

AF XY:

0.00104

AC XY:

115

AN XY:

110460

show subpopulations

Gnomad AFR exome

AF:

0.0224

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000335

Gnomad OTH exome

AF:

0.000380

GnomAD4 exome

AF:

0.000642

AC:

922

AN:

1436608

Hom.:

Cov.:

AF XY:

0.000526

AC XY:

375

AN XY:

712422

show subpopulations

Gnomad4 AFR exome

AF:

0.0228

Gnomad4 AMR exome

AF:

0.00138

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000361

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000173

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.00619

AC:

943

AN:

152340

Hom.:

Cov.:

AF XY:

0.00585

AC XY:

436

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.0217

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00204

Hom.:

Bravo

AF:

0.00708

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

-0.63

CADD

Benign

2.2

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over