Genetic Variant NM_001441.3:c.827-41G>A (chr1-46406203-G-A) – 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.827-41G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0938 in 1,613,836 control chromosomes in the GnomAD database, including 7,920 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 0.070 ( 492 hom., cov: 33)

Exomes 𝑓: 0.096 ( 7428 hom. )

Consequence

FAAH
NM_001441.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0780

Publications

7 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=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.143 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.827-41G>A		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.827-41G>A	intron	N/A	ENSP00000243167.8	O00519
FAAH	ENST00000484697.5	TSL:1	n.71+409G>A	intron	N/A	ENSP00000481641.1	A0A087WYA0
FAAH	ENST00000877148.1		c.827-41G>A	intron	N/A	ENSP00000547207.1

Frequencies

GnomAD3 genomes

AF:

0.0704

AC:

10702

AN:

152114

Hom.:

493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.0681

Gnomad AMR

AF:

0.0620

Gnomad ASJ

AF:

0.113

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.152

Gnomad FIN

AF:

0.0510

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.106

GnomAD2 exomes

AF:

0.0848

AC:

21292

AN:

251216

AF XY:

0.0934

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.0511

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.0514

Gnomad NFE exome

AF:

0.102

Gnomad OTH exome

AF:

0.0985

GnomAD4 exome

AF:

0.0962

AC:

140633

AN:

1461604

Hom.:

7428

Cov.:

AF XY:

0.0988

AC XY:

71861

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.0194

AC:

650

AN:

33480

American (AMR)

AF:

0.0538

AC:

2404

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2810

AN:

26130

East Asian (EAS)

AF:

0.000705

AC:

AN:

39700

South Asian (SAS)

AF:

0.157

AC:

13499

AN:

86252

European-Finnish (FIN)

AF:

0.0556

AC:

2965

AN:

53308

Middle Eastern (MID)

AF:

0.170

AC:

970

AN:

5698

European-Non Finnish (NFE)

AF:

0.100

AC:

111614

AN:

1111932

Other (OTH)

AF:

0.0943

AC:

5693

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

7357

14715

22072

29430

36787

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4032

8064

12096

16128

20160

<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:

0.0703

AC:

10705

AN:

152232

Hom.:

492

Cov.:

AF XY:

0.0698

AC XY:

5197

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0220

AC:

913

AN:

41548

American (AMR)

AF:

0.0619

AC:

947

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

391

AN:

3466

East Asian (EAS)

AF:

0.000965

AC:

AN:

5180

South Asian (SAS)

AF:

0.152

AC:

734

AN:

4818

European-Finnish (FIN)

AF:

0.0510

AC:

541

AN:

10614

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6851

AN:

67986

Other (OTH)

AF:

0.105

AC:

221

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

498

995

1493

1990

2488

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

136

272

408

544

680

<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:

0.0882

Hom.:

127

Bravo

AF:

0.0669

Asia WGS

AF:

0.0550

AC:

190

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.1

(source)

DANN

Benign

0.74

PhyloP100

-0.078

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