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GeneBe

17-82085863-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_004104.5(FASN):c.3741T>C(p.Ala1247=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 1,538,636 control chromosomes in the GnomAD database, including 78,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 6709 hom., cov: 33)
Exomes 𝑓: 0.32 ( 71500 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.426
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-82085863-A-G is Benign according to our data. Variant chr17-82085863-A-G is described in ClinVar as [Benign]. Clinvar id is 1170033.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.426 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FASNNM_004104.5 linkuse as main transcriptc.3741T>C p.Ala1247= synonymous_variant 23/43 ENST00000306749.4
FASNXM_011523538.3 linkuse as main transcriptc.3741T>C p.Ala1247= synonymous_variant 23/43

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FASNENST00000306749.4 linkuse as main transcriptc.3741T>C p.Ala1247= synonymous_variant 23/431 NM_004104.5 P1
FASNENST00000634990.1 linkuse as main transcriptc.3735T>C p.Ala1245= synonymous_variant 23/435

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.288
AC:
43837
AN:
152008
Hom.:
6705
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.228
Gnomad AMI
AF:
0.392
Gnomad AMR
AF:
0.229
Gnomad ASJ
AF:
0.202
Gnomad EAS
AF:
0.294
Gnomad SAS
AF:
0.183
Gnomad FIN
AF:
0.363
Gnomad MID
AF:
0.225
Gnomad NFE
AF:
0.337
Gnomad OTH
AF:
0.291
GnomAD3 exomes
AF:
0.252
AC:
38188
AN:
151766
Hom.:
5228
AF XY:
0.251
AC XY:
20753
AN XY:
82588
show subpopulations
Gnomad AFR exome
AF:
0.220
Gnomad AMR exome
AF:
0.146
Gnomad ASJ exome
AF:
0.190
Gnomad EAS exome
AF:
0.285
Gnomad SAS exome
AF:
0.177
Gnomad FIN exome
AF:
0.350
Gnomad NFE exome
AF:
0.318
Gnomad OTH exome
AF:
0.253
GnomAD4 exome
AF:
0.316
AC:
437494
AN:
1386510
Hom.:
71500
Cov.:
53
AF XY:
0.311
AC XY:
212843
AN XY:
683750
show subpopulations
Gnomad4 AFR exome
AF:
0.220
Gnomad4 AMR exome
AF:
0.155
Gnomad4 ASJ exome
AF:
0.200
Gnomad4 EAS exome
AF:
0.283
Gnomad4 SAS exome
AF:
0.184
Gnomad4 FIN exome
AF:
0.356
Gnomad4 NFE exome
AF:
0.338
Gnomad4 OTH exome
AF:
0.290
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.288
AC:
43848
AN:
152126
Hom.:
6709
Cov.:
33
AF XY:
0.289
AC XY:
21512
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.228
Gnomad4 AMR
AF:
0.228
Gnomad4 ASJ
AF:
0.202
Gnomad4 EAS
AF:
0.294
Gnomad4 SAS
AF:
0.183
Gnomad4 FIN
AF:
0.363
Gnomad4 NFE
AF:
0.337
Gnomad4 OTH
AF:
0.287
Alfa
AF:
0.306
Hom.:
2073
Bravo
AF:
0.276
Asia WGS
AF:
0.197
AC:
685
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Epileptic encephalopathy Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
Cadd
Benign
0.39
Dann
Benign
0.35

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.

Other links and lift over

dbSNP: rs2229422; hg19: chr17-80043739; COSMIC: COSV60755892; COSMIC: COSV60755892; API