Variant rs202024354 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_004104.5(FASN):c.5220C>T(p.Gly1740Gly) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000274 in 1,607,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

FASN
NM_004104.5 splice_region, synonymous

Scores

Splicing: ADA: 0.000006818

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.13

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 17-82083638-G-A is Benign according to our data. Variant chr17-82083638-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 462065.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.13 with no splicing effect.

BS2

High AC in GnomAd4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.5220C>T	p.Gly1740Gly	splice_region_variant, synonymous_variant	31/43	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 linkuse as main transcript	c.5220C>T	p.Gly1740Gly	splice_region_variant, synonymous_variant	31/43		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.5220C>T	p.Gly1740Gly	splice_region_variant, synonymous_variant	31/43	1	NM_004104.5	ENSP00000304592.2		P49327
FASN	ENST00000634990.1 linkuse as main transcript	c.5214C>T	p.Gly1738Gly	splice_region_variant, synonymous_variant	31/43	5		ENSP00000488964.1		A0A0U1RQF0

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000257

AC:

AN:

233366

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

127160

show subpopulations

Gnomad AFR exome

AF:

0.000409

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000213

AC:

AN:

1454654

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

723206

show subpopulations

Gnomad4 AFR exome

AF:

0.000569

Gnomad4 AMR exome

AF:

0.0000916

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.0000853

AC:

AN:

152368

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000240

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000528

Hom.:

Bravo

AF:

0.0000907

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0080

DANN

Benign

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000068

dbscSNV1_RF

Benign

0.0

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