Genetic Variant FAAH:c.1077+127A>G (chr1-46408711-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001441.3(FAAH):c.1077+127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,433,316 control chromosomes in the GnomAD database, including 285,402 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 0.59 ( 27096 hom., cov: 32)

Exomes 𝑓: 0.63 ( 258306 hom. )

Consequence

FAAH
NM_001441.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0880

Publications

35 publications found

Variant links:

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]

FAAH links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 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.1077+127A>G		intron	N/A	NP_001432.2	O00519

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FAAH	ENST00000243167.9	TSL:1 MANE Select	c.1077+127A>G	intron	N/A	ENSP00000243167.8	O00519
FAAH	ENST00000484697.5	TSL:1	n.*50+127A>G	intron	N/A	ENSP00000481641.1	A0A087WYA0
FAAH	ENST00000877148.1		c.1077+127A>G	intron	N/A	ENSP00000547207.1

Frequencies

GnomAD3 genomes

AF:

0.591

AC:

89792

AN:

151898

Hom.:

27106

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.740

Gnomad AMR

AF:

0.600

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.658

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.636

Gnomad OTH

AF:

0.591

GnomAD4 exome

AF:

0.633

AC:

810989

AN:

1281300

Hom.:

258306

AF XY:

0.631

AC XY:

407715

AN XY:

645856

show subpopulations

African (AFR)

AF:

0.452

AC:

13553

AN:

30002

American (AMR)

AF:

0.584

AC:

25618

AN:

43900

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

17288

AN:

24958

East Asian (EAS)

AF:

0.832

AC:

32359

AN:

38886

South Asian (SAS)

AF:

0.577

AC:

47349

AN:

82064

European-Finnish (FIN)

AF:

0.644

AC:

27653

AN:

42966

Middle Eastern (MID)

AF:

0.609

AC:

2369

AN:

3892

European-Non Finnish (NFE)

AF:

0.636

AC:

610291

AN:

959930

Other (OTH)

AF:

0.631

AC:

34509

AN:

54702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

16472

32944

49416

65888

82360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15328

30656

45984

61312

76640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.591

AC:

89804

AN:

152016

Hom.:

27096

Cov.:

AF XY:

0.593

AC XY:

44087

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.457

AC:

18917

AN:

41434

American (AMR)

AF:

0.600

AC:

9170

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

2382

AN:

3472

East Asian (EAS)

AF:

0.821

AC:

4224

AN:

5146

South Asian (SAS)

AF:

0.592

AC:

2851

AN:

4814

European-Finnish (FIN)

AF:

0.658

AC:

6964

AN:

10582

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.636

AC:

43191

AN:

67962

Other (OTH)

AF:

0.585

AC:

1236

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1935

3870

5805

7740

9675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.545

Hom.:

5847

Bravo

AF:

0.583

Asia WGS

AF:

0.701

AC:

2436

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.9

(source)

DANN

Benign

0.45

PhyloP100

-0.088

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over