rs1219884311

Variant names:

• chr1-46394476-G-A
• NM_001441.3:c.128G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-46394476-G-A
• chr1-46394476-G-C
• chr1-46394476-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001441.3(FAAH):​c.128G>A​(p.Arg43Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000807 in 1,238,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R43P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: FAAH NM_001441.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23713833).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAAH	NM_001441.3	c.128G>A	p.Arg43Gln	missense_variant	Exon 1 of 15	ENST00000243167.9	NP_001432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAAH	ENST00000243167.9	c.128G>A	p.Arg43Gln	missense_variant	Exon 1 of 15	1	NM_001441.3	ENSP00000243167.8
FAAH	ENST00000468718.5	n.148G>A		non_coding_transcript_exon_variant	Exon 1 of 5	3
FAAH	ENST00000493735.5	n.106G>A		non_coding_transcript_exon_variant	Exon 1 of 8	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.07e-7 AC: 1 AN: 1238802 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 606910

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.89e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.11
Sift	Benign	0.16	T
Sift4G	Benign	0.32	T
Polyphen		0.99	D
Vest4		0.13
MutPred		0.38		Loss of methylation at R43 (P = 0.0115);
MVP		0.65
MPC		1.1
ClinPred		0.76	D
GERP RS		4.6
Varity_R		0.13
gMVP		0.24

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-46860148;