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GeneBe

1-46406041-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001441.3(FAAH):c.789G>A(p.Lys263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00261 in 1,614,220 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 12 hom., cov: 33)
Exomes 𝑓: 0.0022 ( 36 hom. )

Consequence

FAAH
NM_001441.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.570
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 -13 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=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-46406041-G-A is Benign according to our data. Variant chr1-46406041-G-A is described in ClinVar as [Benign]. Clinvar id is 721205.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=0.57 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 = 0.0066 (1006/152350) while in subpopulation AFR AF= 0.0181 (753/41574). AF 95% confidence interval is 0.017. There are 12 homozygotes in gnomad4. There are 476 alleles in male gnomad4 subpopulation. Median coverage is 33. 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 Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FAAHNM_001441.3 linkuse as main transcriptc.789G>A p.Lys263= synonymous_variant 6/15 ENST00000243167.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FAAHENST00000243167.9 linkuse as main transcriptc.789G>A p.Lys263= synonymous_variant 6/151 NM_001441.3 P1
FAAHENST00000484697.5 linkuse as main transcriptc.72+247G>A intron_variant, NMD_transcript_variant 1
FAAHENST00000489366.2 linkuse as main transcriptn.4G>A non_coding_transcript_exon_variant 1/43
FAAHENST00000493735.5 linkuse as main transcriptn.1010G>A non_coding_transcript_exon_variant 5/85

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00656
AC:
999
AN:
152232
Hom.:
12
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0180
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00170
Gnomad ASJ
AF:
0.00317
Gnomad EAS
AF:
0.0177
Gnomad SAS
AF:
0.0172
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0380
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00812
GnomAD3 exomes
AF:
0.00431
AC:
1084
AN:
251360
Hom.:
15
AF XY:
0.00436
AC XY:
592
AN XY:
135862
show subpopulations
Gnomad AFR exome
AF:
0.0181
Gnomad AMR exome
AF:
0.00147
Gnomad ASJ exome
AF:
0.00367
Gnomad EAS exome
AF:
0.0148
Gnomad SAS exome
AF:
0.0127
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000167
Gnomad OTH exome
AF:
0.00342
GnomAD4 exome
AF:
0.00219
AC:
3207
AN:
1461870
Hom.:
36
Cov.:
59
AF XY:
0.00244
AC XY:
1777
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0199
Gnomad4 AMR exome
AF:
0.00148
Gnomad4 ASJ exome
AF:
0.00432
Gnomad4 EAS exome
AF:
0.0220
Gnomad4 SAS exome
AF:
0.0130
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000953
Gnomad4 OTH exome
AF:
0.00391
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00660
AC:
1006
AN:
152350
Hom.:
12
Cov.:
33
AF XY:
0.00639
AC XY:
476
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0181
Gnomad4 AMR
AF:
0.00170
Gnomad4 ASJ
AF:
0.00317
Gnomad4 EAS
AF:
0.0178
Gnomad4 SAS
AF:
0.0172
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00851
Alfa
AF:
0.00220
Hom.:
2
Bravo
AF:
0.00660
Asia WGS
AF:
0.0130
AC:
46
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000652

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.38
Cadd
Benign
7.3
Dann
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs72480613; hg19: chr1-46871713; API