Variant 17-82085857-G-A 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.3747C>T(p.His1249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,547,626 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.66

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 -11 ACMG points.

BP4

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

BP6

Variant 17-82085857-G-A is Benign according to our data. Variant chr17-82085857-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 531148.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.66 with no splicing effect.

BS2

High AC in GnomAd4 at 120 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FASN	NM_004104.5 linkuse as main transcript	c.3747C>T	p.His1249=	synonymous_variant	23/43	ENST00000306749.4
FASN	XM_011523538.3 linkuse as main transcript	c.3747C>T	p.His1249=	synonymous_variant	23/43

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FASN	ENST00000306749.4 linkuse as main transcript	c.3747C>T	p.His1249=	synonymous_variant	23/43	1	NM_004104.5	P1
FASN	ENST00000634990.1 linkuse as main transcript	c.3741C>T	p.His1247=	synonymous_variant	23/43	5

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000735

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000233

AC:

AN:

158672

Hom.:

AF XY:

0.000173

AC XY:

AN XY:

86492

show subpopulations

Gnomad AFR exome

AF:

0.00281

Gnomad AMR exome

AF:

0.000148

Gnomad ASJ exome

AF:

0.000127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000435

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000596

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000163

AC:

227

AN:

1395354

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

106

AN XY:

688948

show subpopulations

Gnomad4 AFR exome

AF:

0.00339

Gnomad4 AMR exome

AF:

0.0000784

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.0000376

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000803

Gnomad4 OTH exome

AF:

0.000345

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152272

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000693

Hom.:

Bravo

AF:

0.000903

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Invitae

Dec 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.041

DANN

Benign

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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