dbSNP rs4246444: 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.6595+88A>C		intron_variant	Intron 38 of 42	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.6595+88A>C		intron_variant	Intron 38 of 42		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FASN	ENST00000306749.4 link	c.6595+88A>C		intron_variant	Intron 38 of 42	1	NM_004104.5	ENSP00000304592.2		P49327
FASN	ENST00000634990.1 link	c.6589+88A>C		intron_variant	Intron 38 of 42	5		ENSP00000488964.1		A0A0U1RQF0

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over