NM_004104.5:c.4123-10G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004104.5(FASN):c.4123-10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,607,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

FASN
NM_004104.5 intron

Scores

Splicing: ADA: 0.0001412

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -1.19

Publications

0 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 17-82085412-C-T is Benign according to our data. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr17-82085412-C-T is described in CliVar as Likely_benign. Clinvar id is 531114.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FASN	NM_004104.5 link	c.4123-10G>A		intron_variant	Intron 23 of 42	ENST00000306749.4	NP_004095.4	P49327
FASN	XM_011523538.3 link	c.4123-10G>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.4123-10G>A	intron_variant	Intron 23 of 42	1	NM_004104.5	ENSP00000304592.2	P49327
FASN	ENST00000634990.1 link	c.4117-10G>A	intron_variant	Intron 23 of 42	5		ENSP00000488964.1	A0A0U1RQF0
FASN	ENST00000579410.1 link	n.180-10G>A	intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000432

AC:

AN:

231730

AF XY:

0.00000785

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1455406

Hom.:

Cov.:

AF XY:

0.0000207

AC XY:

AN XY:

723618

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33364

American (AMR)

AF:

0.0000226

AC:

AN:

44322

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25994

East Asian (EAS)

AF:

0.0000760

AC:

AN:

39458

South Asian (SAS)

AF:

0.00

AC:

AN:

85400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51374

Middle Eastern (MID)

AF:

0.000734

AC:

AN:

5450

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1109984

Other (OTH)

AF:

0.0000333

AC:

AN:

60060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41566

American (AMR)

AF:

0.00

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

FASN-related disorder

Benign:1

May 22, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Epileptic encephalopathy

Benign:1

Oct 09, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0030

(source)

DANN

Benign

0.79

PhyloP100

-1.2

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.2

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over