1-46406314-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAAH	NM_001441.3	c.897T>C	p.Cys299Cys	synonymous_variant	Exon 7 of 15	ENST00000243167.9	NP_001432.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAAH	ENST00000243167.9	c.897T>C	p.Cys299Cys	synonymous_variant	Exon 7 of 15	1	NM_001441.3	ENSP00000243167.8
FAAH	ENST00000484697.5	n.71+520T>C		intron_variant	Intron 1 of 7	1		ENSP00000481641.1
FAAH	ENST00000489366.2	n.112T>C		non_coding_transcript_exon_variant	Exon 2 of 4	3
FAAH	ENST00000493735.5	n.1118T>C		non_coding_transcript_exon_variant	Exon 6 of 8	5

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

GnomAD3 exomes AF: 0.865 AC: 217498 AN: 251366 Hom.: 94603 AF XY: 0.856 AC XY: 116358 AN XY: 135884

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 SAS exome AF: 0.786

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

Gnomad4 AFR exome AF: 0.856

Gnomad4 AMR exome AF: 0.925

Gnomad4 ASJ exome AF: 0.841

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.785

Gnomad4 FIN exome AF: 0.920

Gnomad4 NFE exome AF: 0.838

Gnomad4 OTH exome AF: 0.853

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

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.907

Gnomad4 ASJ AF: 0.833

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.927

Gnomad4 NFE AF: 0.843

Gnomad4 OTH AF: 0.833

Alfa AF: 0.841 Hom.: 43939

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.8
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs324419; hg19: chr1-46871986; COSMIC: COSV54543498; COSMIC: COSV54543498;