dbSNP rs16968964: AANAT:c.-575-57G>A (chr17-76459190-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 ENST00000250615.7(AANAT):c.-575-57G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.794 in 152,188 control chromosomes in the GnomAD database, including 48,894 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 0.79 ( 48892 hom., cov: 32)

Exomes 𝑓: 0.83 ( 2 hom. )

Consequence

AANAT
ENST00000250615.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.336

Publications

7 publications found

Variant links:

Genes affected

AANAT (HGNC:19): (aralkylamine N-acetyltransferase) The protein encoded by this gene belongs to the acetyltransferase superfamily. It is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. Melatonin is essential for the function of the circadian clock that influences activity and sleep. This enzyme is regulated by cAMP-dependent phosphorylation that promotes its interaction with 14-3-3 proteins and thus protects the enzyme against proteasomal degradation. This gene may contribute to numerous genetic diseases such as delayed sleep phase syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

AANAT 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=-0.82).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000250615.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AANAT	NM_001166579.2		c.-575-57G>A		intron	N/A	NP_001160051.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AANAT	ENST00000250615.7	TSL:1	c.-575-57G>A		intron	N/A	ENSP00000250615.2

Frequencies

GnomAD3 genomes

AF:

0.794

AC:

120737

AN:

152064

Hom.:

48868

Cov.:

show subpopulations

Gnomad AFR

AF:

0.628

Gnomad AMI

AF:

0.776

Gnomad AMR

AF:

0.851

Gnomad ASJ

AF:

0.844

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.914

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.840

Gnomad OTH

AF:

0.798

GnomAD4 exome

AF:

0.833

AC:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.750

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<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:

0.794

AC:

120803

AN:

152182

Hom.:

48892

Cov.:

AF XY:

0.800

AC XY:

59555

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.628

AC:

26058

AN:

41474

American (AMR)

AF:

0.852

AC:

13027

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

2932

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5172

AN:

5176

South Asian (SAS)

AF:

0.913

AC:

4410

AN:

4828

European-Finnish (FIN)

AF:

0.888

AC:

9429

AN:

10614

Middle Eastern (MID)

AF:

0.840

AC:

247

AN:

294

European-Non Finnish (NFE)

AF:

0.840

AC:

57138

AN:

68008

Other (OTH)

AF:

0.799

AC:

1684

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1209

2418

3628

4837

6046

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.813

Hom.:

9704

Bravo

AF:

0.781

Asia WGS

AF:

0.931

AC:

3236

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

2.9

(source)

DANN

Benign

0.50

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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