chr1-46399368-T-C

Position:

• chr1-46399368-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001441.3(FAAH):​c.196-2723T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,126 control chromosomes in the GnomAD database, including 22,801 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 0.53 (22801 hom., cov: 34)
• Consequence: FAAH NM_001441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAAH	NM_001441.3	c.196-2723T>C		intron_variant		ENST00000243167.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAAH	ENST00000243167.9	c.196-2723T>C		intron_variant		1	NM_001441.3	P1
FAAH	ENST00000468718.5	n.216-2723T>C		intron_variant, non_coding_transcript_variant		3
FAAH	ENST00000493735.5	n.174-2723T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81110 AN: 152008 Hom.: 22811 Cov.: 34

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.555

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.533 AC: 81119 AN: 152126 Hom.: 22801 Cov.: 34 AF XY: 0.531 AC XY: 39474 AN XY: 74370

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.673

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.628

Gnomad4 OTH AF: 0.538

Alfa AF: 0.575 Hom.: 5441

Bravo AF: 0.525

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.57

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: rs4141964; hg19: chr1-46865040; COSMIC: COSV54543457;