Variant rs2228309 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004104.5(FASN):c.567T>C(p.Asn189Asn) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.70

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.567T>C	p.Asn189Asn	synonymous_variant	5/43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 linkuse as main transcript	c.567T>C	p.Asn189Asn	synonymous_variant	5/43		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.567T>C	p.Asn189Asn	synonymous_variant	5/43	1	NM_004104.5	ENSP00000304592.2		P49327
FASN	ENST00000634990.1 linkuse as main transcript	c.567T>C	p.Asn189Asn	synonymous_variant	5/43	5		ENSP00000488964.1		A0A0U1RQF0

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77245

AN:

152042

Hom.:

20289

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.538

AC XY:

385474

AN XY:

716888

show subpopulations

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.:

AF XY:

0.502

AC XY:

37342

AN XY:

74388

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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