1-46394398-C-T

Variant names:

• chr1-46394398-C-T
• rs773985381
• NM_001441.3:c.50C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001441.3(FAAH):​c.50C>T​(p.Ala17Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,519,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: FAAH NM_001441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.43
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0152641535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH	NM_001441.3	MANE Select	c.50C>T	p.Ala17Val	missense	Exon 1 of 15	NP_001432.2	O00519

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH	ENST00000243167.9	TSL:1 MANE Select	c.50C>T	p.Ala17Val	missense	Exon 1 of 15	ENSP00000243167.8	O00519
	FAAH	ENST00000877148.1		c.50C>T	p.Ala17Val	missense	Exon 1 of 14	ENSP00000547207.1
	FAAH	ENST00000877151.1		c.50C>T	p.Ala17Val	missense	Exon 1 of 16	ENSP00000547210.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152104 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000286 AC: 37 AN: 129392 AF XY: 0.000231

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00441

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000925

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000109 AC: 149 AN: 1367810 Hom.: 0 Cov.: 30 AF XY: 0.0000989 AC XY: 67 AN XY: 677524

African (AFR) AF: 0.00 AC: 0 AN: 28048

American (AMR) AF: 0.00 AC: 0 AN: 33684

Ashkenazi Jewish (ASJ) AF: 0.00468 AC: 112 AN: 23930

East Asian (EAS) AF: 0.00 AC: 0 AN: 30780

South Asian (SAS) AF: 0.00 AC: 0 AN: 76482

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3960

European-Non Finnish (NFE) AF: 0.0000187 AC: 20 AN: 1071088

Other (OTH) AF: 0.000302 AC: 17 AN: 56338

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152104 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74316

African (AFR) AF: 0.00 AC: 0 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000535 Hom.: 0

Bravo AF: 0.0000982

ExAC AF: 0.000146 AC: 16

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.015	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.039
Sift	Benign	0.070	T
Sift4G	Benign	0.18	T
Polyphen		0.099	B
Vest4		0.42
MutPred		0.27		Loss of MoRF binding (P = 0.1631)
MVP		0.72
MPC		0.45
ClinPred		0.079	T
GERP RS		2.5
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.045
gMVP		0.37
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs773985381; hg19: chr1-46860070;