rs932816

Variant names:

• chr1-46394077-G-A
• rs932816
• NM_001441.3:c.-272G>A

Variant summary

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

The NM_001441.3(FAAH):​c.-272G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 149,916 control chromosomes in the GnomAD database, including 4,289 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 0.23 (4289 hom., cov: 32)
• Consequence: FAAH NM_001441.3 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 21 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAAH	NM_001441.3	c.-272G>A		upstream_gene_variant		ENST00000243167.9	NP_001432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAAH	ENST00000243167.9	c.-272G>A		upstream_gene_variant		1	NM_001441.3	ENSP00000243167.8

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34090 AN: 149794 Hom.: 4289 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.227 AC: 34085 AN: 149916 Hom.: 4289 Cov.: 32 AF XY: 0.223 AC XY: 16341 AN XY: 73292

African (AFR) AF: 0.156 AC: 6155 AN: 39398

American (AMR) AF: 0.187 AC: 2861 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 653 AN: 3464

East Asian (EAS) AF: 0.0209 AC: 108 AN: 5174

South Asian (SAS) AF: 0.108 AC: 520 AN: 4820

European-Finnish (FIN) AF: 0.311 AC: 3289 AN: 10580

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19756 AN: 67926

Other (OTH) AF: 0.220 AC: 460 AN: 2092

Alfa AF: 0.264 Hom.: 7752

Bravo AF: 0.215

Asia WGS AF: 0.0760 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.2
DANN	Benign	0.65
PhyloP100		-0.084
PromoterAI		0.056	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs932816; hg19: chr1-46859749;