Genetic Variant NM_004104.5:c.4122+9G>A (chr17-82085473-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004104.5(FASN):c.4122+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 1,587,466 control chromosomes in the GnomAD database, including 214,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19178 hom., cov: 34)

Exomes 𝑓: 0.52 ( 195424 hom. )

Consequence

FASN
NM_004104.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.26

Publications

10 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 17-82085473-C-T is Benign according to our data. Variant chr17-82085473-C-T is described in ClinVar as Benign. ClinVar VariationId is 1170032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FASN	NM_004104.5	MANE Select	c.4122+9G>A		intron	N/A	NP_004095.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FASN	ENST00000306749.4	TSL:1 MANE Select	c.4122+9G>A	intron	N/A	ENSP00000304592.2	P49327
FASN	ENST00000940344.1		c.4149+9G>A	intron	N/A	ENSP00000610403.1
FASN	ENST00000940346.1		c.4146+9G>A	intron	N/A	ENSP00000610405.1

Frequencies

GnomAD3 genomes

AF:

0.497

AC:

75572

AN:

151946

Hom.:

19154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.521

Gnomad AMR

AF:

0.386

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.383

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.543

Gnomad OTH

AF:

0.486

GnomAD2 exomes

AF:

0.451

AC:

91000

AN:

201830

AF XY:

0.456

show subpopulations

Gnomad AFR exome

AF:

0.508

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.318

Gnomad EAS exome

AF:

0.337

Gnomad FIN exome

AF:

0.539

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.444

GnomAD4 exome

AF:

0.516

AC:

740626

AN:

1435402

Hom.:

195424

Cov.:

AF XY:

0.512

AC XY:

364493

AN XY:

711710

show subpopulations

African (AFR)

AF:

0.501

AC:

16504

AN:

32934

American (AMR)

AF:

0.266

AC:

11033

AN:

41436

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

8231

AN:

25618

East Asian (EAS)

AF:

0.335

AC:

12820

AN:

38250

South Asian (SAS)

AF:

0.395

AC:

32748

AN:

82952

European-Finnish (FIN)

AF:

0.537

AC:

26703

AN:

49746

Middle Eastern (MID)

AF:

0.397

AC:

2138

AN:

5390

European-Non Finnish (NFE)

AF:

0.547

AC:

601963

AN:

1099784

Other (OTH)

AF:

0.480

AC:

28486

AN:

59292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

24351

48702

73054

97405

121756

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16816

33632

50448

67264

84080

<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:

0.497

AC:

75636

AN:

152064

Hom.:

19178

Cov.:

AF XY:

0.494

AC XY:

36729

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.504

AC:

20899

AN:

41486

American (AMR)

AF:

0.385

AC:

5892

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1143

AN:

3472

East Asian (EAS)

AF:

0.337

AC:

1740

AN:

5156

South Asian (SAS)

AF:

0.382

AC:

1847

AN:

4830

European-Finnish (FIN)

AF:

0.531

AC:

5615

AN:

10584

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.543

AC:

36885

AN:

67930

Other (OTH)

AF:

0.488

AC:

1030

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1955

3909

5864

7818

9773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.510

Hom.:

7145

Bravo

AF:

0.484

Asia WGS

AF:

0.367

AC:

1275

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Epileptic encephalopathy (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.046

(source)

DANN

Benign

0.46

PhyloP100

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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