rs41305628

Variant names:

• chr1-46406074-G-A
• rs41305628
• NM_001441.3:c.822G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001441.3(FAAH):​c.822G>A​(p.Glu274Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0439 in 1,614,138 control chromosomes in the GnomAD database, including 1,855 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 0.032 (120 hom., cov: 33)
  • Exomes 𝑓: 0.045 (1735 hom.)
• Consequence: FAAH NM_001441.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157
• Publications: 4 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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0512 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH	NM_001441.3	MANE Select	c.822G>A	p.Glu274Glu	synonymous	Exon 6 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.822G>A	p.Glu274Glu	synonymous	Exon 6 of 15	ENSP00000243167.8	O00519
	FAAH	ENST00000484697.5	TSL:1	n.71+280G>A		intron	N/A	ENSP00000481641.1	A0A087WYA0
	FAAH	ENST00000877148.1		c.822G>A	p.Glu274Glu	synonymous	Exon 6 of 14	ENSP00000547207.1

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4802 AN: 152198 Hom.: 120 Cov.: 33

Gnomad AFR AF: 0.00837

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0258

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0632

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0470

Gnomad OTH AF: 0.0267

GnomAD2 exomes AF: 0.0325 AC: 8168 AN: 251372 AF XY: 0.0329

Gnomad AFR exome AF: 0.00775

Gnomad AMR exome AF: 0.0127

Gnomad ASJ exome AF: 0.0180

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0687

Gnomad NFE exome AF: 0.0462

Gnomad OTH exome AF: 0.0318

GnomAD4 exome AF: 0.0452 AC: 66119 AN: 1461822 Hom.: 1735 Cov.: 59 AF XY: 0.0446 AC XY: 32467 AN XY: 727202

African (AFR) AF: 0.00705 AC: 236 AN: 33480

American (AMR) AF: 0.0136 AC: 610 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0190 AC: 496 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0166 AC: 1430 AN: 86256

European-Finnish (FIN) AF: 0.0673 AC: 3591 AN: 53388

Middle Eastern (MID) AF: 0.00537 AC: 31 AN: 5768

European-Non Finnish (NFE) AF: 0.0516 AC: 57367 AN: 1111976

Other (OTH) AF: 0.0390 AC: 2357 AN: 60394

GnomAD4 genome AF: 0.0315 AC: 4800 AN: 152316 Hom.: 120 Cov.: 33 AF XY: 0.0321 AC XY: 2391 AN XY: 74476

African (AFR) AF: 0.00835 AC: 347 AN: 41570

American (AMR) AF: 0.0258 AC: 395 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5182

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4832

European-Finnish (FIN) AF: 0.0632 AC: 671 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0469 AC: 3193 AN: 68016

Other (OTH) AF: 0.0265 AC: 56 AN: 2116

Alfa AF: 0.0393 Hom.: 111

Bravo AF: 0.0284

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0414

EpiControl AF: 0.0424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.40
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: -36

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

Other links and lift over

dbSNP: rs41305628; hg19: chr1-46871746; COSMIC: COSV54543853; COSMIC: COSV54543853;