rs11576941

Variant names:

• chr1-46409395-G-T
• rs11576941
• NM_001441.3:c.1175+197G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001441.3(FAAH):​c.1175+197G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 598,906 control chromosomes in the GnomAD database, including 29,125 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 0.27 (6375 hom., cov: 31)
  • Exomes 𝑓: 0.31 (22750 hom.)
• Consequence: FAAH NM_001441.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.552
• Publications: 19 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 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.1175+197G>T		intron	N/A	NP_001432.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAAH	ENST00000243167.9	TSL:1 MANE Select	c.1175+197G>T		intron	N/A	ENSP00000243167.8
	FAAH	ENST00000484697.5	TSL:1	n.*148+197G>T		intron	N/A	ENSP00000481641.1
	FAAH	ENST00000877148.1		c.1175+197G>T		intron	N/A	ENSP00000547207.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41610 AN: 151624 Hom.: 6380 Cov.: 31

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.447

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.310 AC: 138832 AN: 447162 Hom.: 22750 AF XY: 0.305 AC XY: 73689 AN XY: 241310

African (AFR) AF: 0.158 AC: 2042 AN: 12936

American (AMR) AF: 0.387 AC: 11283 AN: 29170

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 6773 AN: 15180

East Asian (EAS) AF: 0.472 AC: 12364 AN: 26218

South Asian (SAS) AF: 0.226 AC: 12589 AN: 55678

European-Finnish (FIN) AF: 0.250 AC: 6676 AN: 26734

Middle Eastern (MID) AF: 0.348 AC: 659 AN: 1894

European-Non Finnish (NFE) AF: 0.308 AC: 78570 AN: 255048

Other (OTH) AF: 0.324 AC: 7876 AN: 24304

GnomAD4 genome AF: 0.274 AC: 41599 AN: 151744 Hom.: 6375 Cov.: 31 AF XY: 0.273 AC XY: 20270 AN XY: 74124

African (AFR) AF: 0.156 AC: 6448 AN: 41322

American (AMR) AF: 0.342 AC: 5209 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 1550 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2479 AN: 5072

South Asian (SAS) AF: 0.238 AC: 1132 AN: 4766

European-Finnish (FIN) AF: 0.248 AC: 2619 AN: 10580

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21015 AN: 67974

Other (OTH) AF: 0.295 AC: 621 AN: 2104

Alfa AF: 0.301 Hom.: 27274

Bravo AF: 0.279

Asia WGS AF: 0.367 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.79
PhyloP100		0.55
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: rs11576941; hg19: chr1-46875067; COSMIC: COSV54543518; COSMIC: COSV54543518;