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rs324420

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001441.3(FAAH):c.385C>A(p.Pro129Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,613,776 control chromosomes in the GnomAD database, including 41,065 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5577 hom., cov: 33)
Exomes 𝑓: 0.22 ( 35488 hom. )

Consequence

FAAH
NM_001441.3 missense

Scores

18

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.386
Variant links:
Genes affected
FAAH (HGNC:3553): (fatty acid amide hydrolase) This gene encodes a protein that is responsible for the hydrolysis of a number of primary and secondary fatty acid amides, including the neuromodulatory compounds anandamide and oleamide. [provided by RefSeq, Jul 2008]

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 (MetaRNN=0.0037901402).
BP6
Variant 1-46405089-C-A is Benign according to our data. Variant chr1-46405089-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 6724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAAHNM_001441.3 linkuse as main transcriptc.385C>A p.Pro129Thr missense_variant 3/15 ENST00000243167.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAAHENST00000243167.9 linkuse as main transcriptc.385C>A p.Pro129Thr missense_variant 3/151 NM_001441.3 P1
FAAHENST00000468718.5 linkuse as main transcriptn.405C>A non_coding_transcript_exon_variant 3/53
FAAHENST00000493735.5 linkuse as main transcriptn.363C>A non_coding_transcript_exon_variant 3/85

Frequencies

GnomAD3 genomes
AF:
0.260
AC:
39514
AN:
152014
Hom.:
5570
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.359
Gnomad AMI
AF:
0.145
Gnomad AMR
AF:
0.303
Gnomad ASJ
AF:
0.147
Gnomad EAS
AF:
0.176
Gnomad SAS
AF:
0.196
Gnomad FIN
AF:
0.278
Gnomad MID
AF:
0.143
Gnomad NFE
AF:
0.207
Gnomad OTH
AF:
0.237
GnomAD3 exomes
AF:
0.236
AC:
59345
AN:
251362
Hom.:
7639
AF XY:
0.225
AC XY:
30632
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.358
Gnomad AMR exome
AF:
0.345
Gnomad ASJ exome
AF:
0.148
Gnomad EAS exome
AF:
0.170
Gnomad SAS exome
AF:
0.199
Gnomad FIN exome
AF:
0.286
Gnomad NFE exome
AF:
0.205
Gnomad OTH exome
AF:
0.226
GnomAD4 exome
AF:
0.215
AC:
314560
AN:
1461644
Hom.:
35488
Cov.:
40
AF XY:
0.214
AC XY:
155434
AN XY:
727132
show subpopulations
Gnomad4 AFR exome
AF:
0.364
Gnomad4 AMR exome
AF:
0.340
Gnomad4 ASJ exome
AF:
0.149
Gnomad4 EAS exome
AF:
0.167
Gnomad4 SAS exome
AF:
0.199
Gnomad4 FIN exome
AF:
0.284
Gnomad4 NFE exome
AF:
0.207
Gnomad4 OTH exome
AF:
0.221
GnomAD4 genome
AF:
0.260
AC:
39553
AN:
152132
Hom.:
5577
Cov.:
33
AF XY:
0.261
AC XY:
19409
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.359
Gnomad4 AMR
AF:
0.304
Gnomad4 ASJ
AF:
0.147
Gnomad4 EAS
AF:
0.176
Gnomad4 SAS
AF:
0.196
Gnomad4 FIN
AF:
0.278
Gnomad4 NFE
AF:
0.207
Gnomad4 OTH
AF:
0.239
Alfa
AF:
0.207
Hom.:
8871
Bravo
AF:
0.267
TwinsUK
AF:
0.206
AC:
765
ALSPAC
AF:
0.190
AC:
731
ESP6500AA
AF:
0.348
AC:
1533
ESP6500EA
AF:
0.200
AC:
1722
ExAC
AF:
0.233
AC:
28288
Asia WGS
AF:
0.192
AC:
669
AN:
3478
EpiCase
AF:
0.193
EpiControl
AF:
0.189

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

FAAH-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 18, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Polysubstance abuse, susceptibility to Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsOct 08, 2021- -
FAAH POLYMORPHISM Benign:1
Benign, no assertion criteria providedliterature onlyOMIMApr 01, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.63
T
BayesDel_noAF
Benign
-0.54
Cadd
Benign
13
Dann
Benign
0.59
DEOGEN2
Benign
0.044
T
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.66
T
MetaRNN
Benign
0.0038
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
1.3
L
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-0.34
N
REVEL
Benign
0.061
Sift
Benign
0.32
T
Sift4G
Benign
0.46
T
Polyphen
0.014
B
Vest4
0.035
MPC
1.2
ClinPred
0.0028
T
GERP RS
3.1
Varity_R
0.12
gMVP
0.56

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: rs324420; hg19: chr1-46870761; COSMIC: COSV54544102; COSMIC: COSV54544102; API