dbSNP rs576100145: FASN:p.Thr1698Thr (chr17-82083979-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_004104.5(FASN):c.5094C>T(p.Thr1698Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,540,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.121

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

FASN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 17-82083979-G-A is Benign according to our data. Variant chr17-82083979-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 531153.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.121 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004104.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	NM_004104.5	MANE Select	c.5094C>T	p.Thr1698Thr	synonymous	Exon 29 of 43	NP_004095.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FASN	ENST00000306749.4	TSL:1 MANE Select	c.5094C>T	p.Thr1698Thr	synonymous	Exon 29 of 43	ENSP00000304592.2	P49327
FASN	ENST00000940344.1		c.5121C>T	p.Thr1707Thr	synonymous	Exon 29 of 43	ENSP00000610403.1
FASN	ENST00000940346.1		c.5118C>T	p.Thr1706Thr	synonymous	Exon 29 of 43	ENSP00000610405.1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000710

AC:

AN:

140768

AF XY:

0.0000661

show subpopulations

Gnomad AFR exome

AF:

0.000133

Gnomad AMR exome

AF:

0.0000816

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000934

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000740

Gnomad OTH exome

AF:

0.000239

GnomAD4 exome

AF:

0.0000569

AC:

AN:

1388412

Hom.:

Cov.:

AF XY:

0.0000643

AC XY:

AN XY:

684824

show subpopulations

African (AFR)

AF:

0.000127

AC:

AN:

31526

American (AMR)

AF:

0.0000842

AC:

AN:

35612

Ashkenazi Jewish (ASJ)

AF:

0.0000398

AC:

AN:

25096

East Asian (EAS)

AF:

0.0000840

AC:

AN:

35694

South Asian (SAS)

AF:

0.0000632

AC:

AN:

79148

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.0000557

AC:

AN:

1077790

Other (OTH)

AF:

0.0000519

AC:

AN:

57800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41582

American (AMR)

AF:

0.000131

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000769

Hom.:

Bravo

AF:

0.000110

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epileptic encephalopathy (1)

FASN-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.6

(source)

DANN

Benign

0.90

PhyloP100

-0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over