rs4238989

Variant names:

• chr17-76467306-C-G
• rs4238989
• ENST00000250615.7:c.60+1074C>G

Variant summary

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

The ENST00000250615.7(AANAT):​c.60+1074C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,044 control chromosomes in the GnomAD database, including 17,012 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 0.45 (17012 hom., cov: 32)
• Consequence: AANAT ENST00000250615.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AANAT	NM_001166579.2	c.60+1074C>G		intron_variant	Intron 4 of 6		NP_001160051.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AANAT	ENST00000250615.7	c.60+1074C>G		intron_variant	Intron 4 of 6	1		ENSP00000250615.2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68997 AN: 151926 Hom.: 17011 Cov.: 32

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.428

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.454 AC: 69008 AN: 152044 Hom.: 17012 Cov.: 32 AF XY: 0.458 AC XY: 34005 AN XY: 74322

African (AFR) AF: 0.239 AC: 9915 AN: 41456

American (AMR) AF: 0.518 AC: 7918 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 1765 AN: 3472

East Asian (EAS) AF: 0.428 AC: 2214 AN: 5176

South Asian (SAS) AF: 0.485 AC: 2336 AN: 4816

European-Finnish (FIN) AF: 0.602 AC: 6364 AN: 10568

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36938 AN: 67966

Other (OTH) AF: 0.466 AC: 984 AN: 2110

Alfa AF: 0.497 Hom.: 2447

Bravo AF: 0.437

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.0
DANN	Benign	0.65
PhyloP100		-0.14
PromoterAI		0.021	Neutral
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: rs4238989; hg19: chr17-74463388;