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

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.4122+9G>A		intron_variant	Intron 23 of 42	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.4122+9G>A		intron_variant	Intron 23 of 42		XP_011521840.1	P49327

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FASN	ENST00000306749.4 link	c.4122+9G>A	intron_variant	Intron 23 of 42	1	NM_004104.5	ENSP00000304592.2	P49327
FASN	ENST00000634990.1 link	c.4116+9G>A	intron_variant	Intron 23 of 42	5		ENSP00000488964.1	A0A0U1RQF0
FASN	ENST00000579410.1 link	n.179+9G>A	intron_variant	Intron 1 of 1	2

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

GnomAD3 exomes

AF:

0.451

AC:

91000

AN:

201830

Hom.:

21668

AF XY:

0.456

AC XY:

50370

AN XY:

110358

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 SAS exome

AF:

0.401

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

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.321

Gnomad4 EAS exome

AF:

0.335

Gnomad4 SAS exome

AF:

0.395

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.547

Gnomad4 OTH exome

AF:

0.480

GnomAD4 genome

AF:

0.497

AC:

75636

AN:

152064

Hom.:

19178

Cov.:

AF XY:

0.494

AC XY:

36729

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.504

Gnomad4 AMR

AF:

0.385

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.337

Gnomad4 SAS

AF:

0.382

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.543

Gnomad4 OTH

AF:

0.488

Alfa

AF:

0.510

Hom.:

7145

Bravo

AF:

0.484

Asia WGS

AF:

0.367

AC:

1275

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.046

DANN

Benign

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over