Genetic Variant FASN:c.-8+672G>A (chr17-82097449-C-T) – 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.-8+672G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,344 control chromosomes in the GnomAD database, including 5,118 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 0.24 ( 5114 hom., cov: 35)

Exomes 𝑓: 0.35 ( 4 hom. )

Consequence

FASN
NM_004104.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0610

Publications

5 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=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 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.-8+672G>A		intron	N/A	NP_004095.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FASN	ENST00000306749.4	TSL:1 MANE Select	c.-8+672G>A	intron	N/A	ENSP00000304592.2
FASN	ENST00000940344.1		c.-8+672G>A	intron	N/A	ENSP00000610403.1
FASN	ENST00000940346.1		c.-8+672G>A	intron	N/A	ENSP00000610405.1

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36402

AN:

152144

Hom.:

5115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.124

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.211

Gnomad EAS

AF:

0.0639

Gnomad SAS

AF:

0.193

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.323

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.345

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.346

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.239

AC:

36400

AN:

152260

Hom.:

5114

Cov.:

AF XY:

0.238

AC XY:

17743

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.124

AC:

5149

AN:

41564

American (AMR)

AF:

0.205

AC:

3143

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.211

AC:

731

AN:

3472

East Asian (EAS)

AF:

0.0643

AC:

333

AN:

5182

South Asian (SAS)

AF:

0.194

AC:

937

AN:

4832

European-Finnish (FIN)

AF:

0.305

AC:

3236

AN:

10608

Middle Eastern (MID)

AF:

0.240

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.323

AC:

21935

AN:

67978

Other (OTH)

AF:

0.248

AC:

525

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1472

2943

4415

5886

7358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.281

Hom.:

795

Bravo

AF:

0.225

Asia WGS

AF:

0.113

AC:

394

AN:

3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.4

(source)

DANN

Benign

0.91

PhyloP100

-0.061

PromoterAI

-0.17

Neutral

(source)

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over