rs324418

Variant names:

• chr1-46407026-A-G
• rs324418
• NM_001441.3:c.951+658A>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.951+658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 151,578 control chromosomes in the GnomAD database, including 6,495 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 0.28 (6495 hom., cov: 30)
• Consequence: FAAH NM_001441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.232
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAAH	NM_001441.3	c.951+658A>G		intron_variant	Intron 7 of 14	ENST00000243167.9	NP_001432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAAH	ENST00000243167.9	c.951+658A>G		intron_variant	Intron 7 of 14	1	NM_001441.3	ENSP00000243167.8
FAAH	ENST00000484697.5	n.71+1232A>G		intron_variant	Intron 1 of 7	1		ENSP00000481641.1
FAAH	ENST00000489366.2	n.166+658A>G		intron_variant	Intron 2 of 3	3
FAAH	ENST00000493735.5	n.1172+658A>G		intron_variant	Intron 6 of 7	5

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42847 AN: 151464 Hom.: 6488 Cov.: 30

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.283 AC: 42886 AN: 151578 Hom.: 6495 Cov.: 30 AF XY: 0.286 AC XY: 21167 AN XY: 74056

African (AFR) AF: 0.377 AC: 15625 AN: 41414

American (AMR) AF: 0.318 AC: 4859 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3470

East Asian (EAS) AF: 0.182 AC: 900 AN: 4934

South Asian (SAS) AF: 0.231 AC: 1107 AN: 4796

European-Finnish (FIN) AF: 0.345 AC: 3643 AN: 10558

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.227 AC: 15388 AN: 67826

Other (OTH) AF: 0.255 AC: 539 AN: 2112

Alfa AF: 0.288 Hom.: 1195

Bravo AF: 0.285

Asia WGS AF: 0.204 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.62
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs324418; hg19: chr1-46872698;