1-46406074-G-A

Position:

• chr1-46406074-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000243167.9(FAAH):​c.822G>A​(p.Glu274=) 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 ENST00000243167.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.157

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 Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAAH	NM_001441.3	c.822G>A	p.Glu274=	synonymous_variant	6/15	ENST00000243167.9	NP_001432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAAH	ENST00000243167.9	c.822G>A	p.Glu274=	synonymous_variant	6/15	1	NM_001441.3	ENSP00000243167	P1
FAAH	ENST00000484697.5	c.72+280G>A		intron_variant, NMD_transcript_variant		1		ENSP00000481641
FAAH	ENST00000489366.2	n.37G>A		non_coding_transcript_exon_variant	1/4	3
FAAH	ENST00000493735.5	n.1043G>A		non_coding_transcript_exon_variant	5/8	5

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

GnomAD3 exomes AF: 0.0325 AC: 8168 AN: 251372 Hom.: 188 AF XY: 0.0329 AC XY: 4465 AN XY: 135860

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 SAS exome AF: 0.0157

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

Gnomad4 AFR exome AF: 0.00705

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.0190

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0673

Gnomad4 NFE exome AF: 0.0516

Gnomad4 OTH exome AF: 0.0390

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

Gnomad4 AFR AF: 0.00835

Gnomad4 AMR AF: 0.0258

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0632

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.0398 Hom.: 97

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	12
DANN	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

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