Genetic Variant FASN:c.6595+88A>C (chr17-82081076-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004104.5(FASN):c.6595+88A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,475,934 control chromosomes in the GnomAD database, including 390,728 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.74 ( 42169 hom., cov: 34)

Exomes 𝑓: 0.72 ( 348559 hom. )

Consequence

FASN
NM_004104.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.204

Publications

25 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	NM_004104.5	MANE Select	c.6595+88A>C		intron	N/A	NP_004095.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	ENST00000306749.4	TSL:1 MANE Select	c.6595+88A>C		intron	N/A	ENSP00000304592.2
	FASN	ENST00000634990.1	TSL:5	c.6589+88A>C		intron	N/A	ENSP00000488964.1

Frequencies

GnomAD3 genomes

AF:

0.740

AC:

112502

AN:

152022

Hom.:

42120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.794

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.754

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.750

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.745

Gnomad OTH

AF:

0.734

GnomAD4 exome

AF:

0.722

AC:

955637

AN:

1323794

Hom.:

348559

Cov.:

AF XY:

0.715

AC XY:

469355

AN XY:

656122

show subpopulations

African (AFR)

AF:

0.795

AC:

24110

AN:

30318

American (AMR)

AF:

0.736

AC:

26220

AN:

35604

Ashkenazi Jewish (ASJ)

AF:

0.603

AC:

14905

AN:

24734

East Asian (EAS)

AF:

0.435

AC:

15431

AN:

35512

South Asian (SAS)

AF:

0.566

AC:

44070

AN:

77916

European-Finnish (FIN)

AF:

0.755

AC:

29532

AN:

39100

Middle Eastern (MID)

AF:

0.679

AC:

2793

AN:

4116

European-Non Finnish (NFE)

AF:

0.744

AC:

759627

AN:

1020992

Other (OTH)

AF:

0.702

AC:

38949

AN:

55502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

14025

28051

42076

56102

70127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18376

36752

55128

73504

91880

<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:

0.740

AC:

112607

AN:

152140

Hom.:

42169

Cov.:

AF XY:

0.736

AC XY:

54721

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.794

AC:

32943

AN:

41492

American (AMR)

AF:

0.754

AC:

11531

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2104

AN:

3472

East Asian (EAS)

AF:

0.433

AC:

2236

AN:

5162

South Asian (SAS)

AF:

0.559

AC:

2700

AN:

4826

European-Finnish (FIN)

AF:

0.750

AC:

7949

AN:

10592

Middle Eastern (MID)

AF:

0.690

AC:

203

AN:

294

European-Non Finnish (NFE)

AF:

0.745

AC:

50681

AN:

67986

Other (OTH)

AF:

0.735

AC:

1549

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1532

3065

4597

6130

7662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

838

1676

2514

3352

4190

<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:

0.735

Hom.:

151312

Bravo

AF:

0.744

Asia WGS

AF:

0.568

AC:

1977

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.9

(source)

DANN

Benign

0.42

PhyloP100

-0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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