1-46406314-T-C

Variant names:

• chr1-46406314-T-C
• rs324419
• NM_001441.3:c.897T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001441.3(FAAH):​c.897T>C​(p.Cys299Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,614,010 control chromosomes in the GnomAD database, including 581,262 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 0.86 (56762 hom., cov: 33)
  • Exomes 𝑓: 0.85 (524500 hom.)
• Consequence: FAAH NM_001441.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 42 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP7: Synonymous conserved (PhyloP=-0.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.897T>C	p.Cys299Cys	synonymous	Exon 7 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.897T>C	p.Cys299Cys	synonymous	Exon 7 of 15	ENSP00000243167.8	O00519
	FAAH	ENST00000484697.5	TSL:1	n.71+520T>C		intron	N/A	ENSP00000481641.1	A0A087WYA0
	FAAH	ENST00000877148.1		c.897T>C	p.Cys299Cys	synonymous	Exon 7 of 14	ENSP00000547207.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131353 AN: 152172 Hom.: 56750 Cov.: 33

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.833

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.843

Gnomad OTH AF: 0.838

GnomAD2 exomes AF: 0.865 AC: 217498 AN: 251366 AF XY: 0.856

Gnomad AFR exome AF: 0.856

Gnomad AMR exome AF: 0.930

Gnomad ASJ exome AF: 0.840

Gnomad EAS exome AF: 0.997

Gnomad FIN exome AF: 0.925

Gnomad NFE exome AF: 0.838

Gnomad OTH exome AF: 0.860

GnomAD4 exome AF: 0.846 AC: 1236802 AN: 1461720 Hom.: 524500 Cov.: 66 AF XY: 0.844 AC XY: 613484 AN XY: 727174

African (AFR) AF: 0.856 AC: 28675 AN: 33480

American (AMR) AF: 0.925 AC: 41367 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 21976 AN: 26136

East Asian (EAS) AF: 0.999 AC: 39655 AN: 39700

South Asian (SAS) AF: 0.785 AC: 67712 AN: 86258

European-Finnish (FIN) AF: 0.920 AC: 49018 AN: 53296

Middle Eastern (MID) AF: 0.782 AC: 4508 AN: 5768

European-Non Finnish (NFE) AF: 0.838 AC: 932348 AN: 1111966

Other (OTH) AF: 0.853 AC: 51543 AN: 60394

GnomAD4 genome AF: 0.863 AC: 131413 AN: 152290 Hom.: 56762 Cov.: 33 AF XY: 0.865 AC XY: 64448 AN XY: 74478

African (AFR) AF: 0.857 AC: 35627 AN: 41556

American (AMR) AF: 0.907 AC: 13883 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 2891 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5154 AN: 5166

South Asian (SAS) AF: 0.799 AC: 3857 AN: 4828

European-Finnish (FIN) AF: 0.927 AC: 9853 AN: 10628

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.843 AC: 57315 AN: 68022

Other (OTH) AF: 0.833 AC: 1763 AN: 2116

Alfa AF: 0.843 Hom.: 115655

Bravo AF: 0.864

Asia WGS AF: 0.902 AC: 3135 AN: 3478

EpiCase AF: 0.834

EpiControl AF: 0.840

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.50
PhyloP100		-0.030
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: rs324419; hg19: chr1-46871986; COSMIC: COSV54543498; COSMIC: COSV54543498;