15-88623530-T-G

Variant names:

• chr15-88623530-T-G
• rs2028389
• NM_022767.4:c.-65+2148T>G

Variant summary

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

The NM_022767.4(AEN):​c.-65+2148T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,152 control chromosomes in the GnomAD database, including 43,674 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 0.73 (43674 hom., cov: 33)
• Consequence: AEN NM_022767.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• Publications: 1 publications found

Genes affected

AEN (HGNC:25722): (apoptosis enhancing nuclease) Enables exonuclease activity. Involved in intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator and response to ionizing radiation. Located in nuclear membrane; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AEN	NM_022767.4	c.-65+2148T>G		intron_variant	Intron 1 of 3	ENST00000332810.4	NP_073604.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AEN	ENST00000332810.4	c.-65+2148T>G		intron_variant	Intron 1 of 3	1	NM_022767.4	ENSP00000331944.3

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111546 AN: 152034 Hom.: 43660 Cov.: 33

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.917

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.793

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.761

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.733 AC: 111599 AN: 152152 Hom.: 43674 Cov.: 33 AF XY: 0.734 AC XY: 54635 AN XY: 74384

African (AFR) AF: 0.441 AC: 18278 AN: 41488

American (AMR) AF: 0.757 AC: 11579 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.886 AC: 3075 AN: 3472

East Asian (EAS) AF: 0.794 AC: 4104 AN: 5172

South Asian (SAS) AF: 0.740 AC: 3565 AN: 4820

European-Finnish (FIN) AF: 0.869 AC: 9206 AN: 10598

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.869 AC: 59109 AN: 67984

Other (OTH) AF: 0.767 AC: 1622 AN: 2116

Alfa AF: 0.820 Hom.: 52321

Bravo AF: 0.713

Asia WGS AF: 0.702 AC: 2442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.0
DANN	Benign	0.49
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2028389; hg19: chr15-89166761;