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rs115212667

chr17-82092928-G-Achr17-82092928-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_004104.5(FASN):c.747C>T(p.Ala249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 1,606,862 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. A249A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0063 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00075 ( 14 hom. )

Consequence

FASN
NM_004104.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.55
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]

Genome browser will be placed here

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=-0.76).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-82092928-G-A is Benign according to our data. Variant chr17-82092928-G-A is described in ClinVar as [Benign]. Clinvar id is 462113.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=-5.55 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00633 (964/152312) while in subpopulation AFR AF= 0.022 (916/41560). AF 95% confidence interval is 0.0209. There are 6 homozygotes in gnomad4. There are 479 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 964 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FASNNM_004104.5 linkuse as main transcriptc.747C>T p.Ala249= synonymous_variant 6/43 ENST00000306749.4
FASNXM_011523538.3 linkuse as main transcriptc.747C>T p.Ala249= synonymous_variant 6/43

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FASNENST00000306749.4 linkuse as main transcriptc.747C>T p.Ala249= synonymous_variant 6/431 NM_004104.5 P1
FASNENST00000634990.1 linkuse as main transcriptc.747C>T p.Ala249= synonymous_variant 6/435

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00633
AC:
964
AN:
152194
Hom.:
6
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0221
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00229
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00334
GnomAD3 exomes
AF:
0.00170
AC:
401
AN:
235390
Hom.:
5
AF XY:
0.00132
AC XY:
169
AN XY:
127900
show subpopulations
Gnomad AFR exome
AF:
0.0233
Gnomad AMR exome
AF:
0.00123
Gnomad ASJ exome
AF:
0.000105
Gnomad EAS exome
AF:
0.0000566
Gnomad SAS exome
AF:
0.000308
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000474
Gnomad OTH exome
AF:
0.000695
GnomAD4 exome
AF:
0.000748
AC:
1088
AN:
1454550
Hom.:
14
Cov.:
36
AF XY:
0.000645
AC XY:
466
AN XY:
722908
show subpopulations
Gnomad4 AFR exome
AF:
0.0259
Gnomad4 AMR exome
AF:
0.00123
Gnomad4 ASJ exome
AF:
0.0000387
Gnomad4 EAS exome
AF:
0.000127
Gnomad4 SAS exome
AF:
0.000294
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.00175
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00633
AC:
964
AN:
152312
Hom.:
6
Cov.:
33
AF XY:
0.00643
AC XY:
479
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0220
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00222
Hom.:
3
Bravo
AF:
0.00709
Asia WGS
AF:
0.00144
AC:
5
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 testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
Cadd
Benign
0.34
Dann
Benign
0.75

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: rs115212667; hg19: chr17-80050804; API