ENST00000250615.7:c.-575-661C>T

Variant names:

• chr17-76458586-C-T
• rs11077820
• ENST00000250615.7:c.-575-661C>T

Variant summary

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

The ENST00000250615.7(AANAT):​c.-575-661C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 152,062 control chromosomes in the GnomAD database, including 24,075 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 0.54 (24075 hom., cov: 32)
• Consequence: AANAT ENST00000250615.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.603
• Publications: 11 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AANAT	NM_001166579.2	c.-575-661C>T		intron_variant	Intron 1 of 6		NP_001160051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AANAT	ENST00000250615.7	c.-575-661C>T		intron_variant	Intron 1 of 6	1		ENSP00000250615.2

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82636 AN: 151944 Hom.: 24073 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.544 AC: 82655 AN: 152062 Hom.: 24075 Cov.: 32 AF XY: 0.551 AC XY: 40956 AN XY: 74318

African (AFR) AF: 0.315 AC: 13050 AN: 41456

American (AMR) AF: 0.583 AC: 8903 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2629 AN: 5172

South Asian (SAS) AF: 0.674 AC: 3243 AN: 4812

European-Finnish (FIN) AF: 0.752 AC: 7968 AN: 10590

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.635 AC: 43193 AN: 67978

Other (OTH) AF: 0.545 AC: 1146 AN: 2104

Alfa AF: 0.601 Hom.: 46508

Bravo AF: 0.518

Asia WGS AF: 0.574 AC: 1995 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.52
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11077820; hg19: chr17-74454668;