1-46399999-A-G

Variant names:

• chr1-46399999-A-G
• rs3766246
• NM_001441.3:c.196-2092A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001441.3(FAAH):​c.196-2092A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,936 control chromosomes in the GnomAD database, including 22,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (22028 hom., cov: 31)
• Consequence: FAAH NM_001441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 28 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH	NM_001441.3	MANE Select	c.196-2092A>G		intron	N/A	NP_001432.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH	ENST00000243167.9	TSL:1 MANE Select	c.196-2092A>G		intron	N/A	ENSP00000243167.8
	FAAH	ENST00000468718.5	TSL:3	n.216-2092A>G		intron	N/A
	FAAH	ENST00000493735.5	TSL:5	n.174-2092A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78677 AN: 151820 Hom.: 22039 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.539

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.518 AC: 78677 AN: 151936 Hom.: 22028 Cov.: 31 AF XY: 0.515 AC XY: 38252 AN XY: 74222

African (AFR) AF: 0.294 AC: 12152 AN: 41384

American (AMR) AF: 0.548 AC: 8377 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2337 AN: 3466

East Asian (EAS) AF: 0.508 AC: 2619 AN: 5154

South Asian (SAS) AF: 0.375 AC: 1809 AN: 4820

European-Finnish (FIN) AF: 0.636 AC: 6707 AN: 10552

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42690 AN: 67964

Other (OTH) AF: 0.532 AC: 1122 AN: 2110

Alfa AF: 0.588 Hom.: 101850

Bravo AF: 0.507

Asia WGS AF: 0.447 AC: 1554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.9
DANN	Benign	0.90
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3766246; hg19: chr1-46865671; COSMIC: COSV54543487;