Genetic Variant NM_004104.5:c.3747C>T (chr17-82085857-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_004104.5(FASN):c.3747C>T(p.His1249His) 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

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: Benign. The variant received -7 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 VariationId is 531148.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.66 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.3747C>T	p.His1249His	synonymous	Exon 23 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.3747C>T	p.His1249His	synonymous	Exon 23 of 43	ENSP00000304592.2	P49327
FASN	ENST00000940344.1		c.3774C>T	p.His1258His	synonymous	Exon 23 of 43	ENSP00000610403.1
FASN	ENST00000940346.1		c.3771C>T	p.His1257His	synonymous	Exon 23 of 43	ENSP00000610405.1

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

GnomAD2 exomes

AF:

0.000233

AC:

AN:

158672

AF XY:

0.000173

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 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

African (AFR)

AF:

0.00339

AC:

110

AN:

32410

American (AMR)

AF:

0.0000784

AC:

AN:

38286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24788

East Asian (EAS)

AF:

0.0000268

AC:

AN:

37278

South Asian (SAS)

AF:

0.0000376

AC:

AN:

79688

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35442

Middle Eastern (MID)

AF:

0.000562

AC:

AN:

5338

European-Non Finnish (NFE)

AF:

0.0000803

AC:

AN:

1084078

Other (OTH)

AF:

0.000345

AC:

AN:

58046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.000788

AC:

120

AN:

152272

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00265

AC:

110

AN:

41568

American (AMR)

AF:

0.000131

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67992

Other (OTH)

AF:

0.000947

AC:

AN:

2112

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

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:

0.000693

Hom.:

Bravo

AF:

0.000903

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epileptic encephalopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.041

(source)

DANN

Benign

0.26

PhyloP100

-2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=85/15

polymorphism

(source)

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

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