rs41276930

Positions:

• chr15-88611842-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The XM_017022489.2(AEN):​c.-65+3000C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00664 in 519,372 control chromosomes in the GnomAD database, including 53 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 0.0049 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0073 (48 hom.)
• Consequence: AEN XM_017022489.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67

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]

MIR7-2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AEN	XM_017022489.2	c.-65+3000C>T		intron_variant			XP_016877978.1
AEN	XM_047432946.1	c.-65+3000C>T		intron_variant			XP_047288902.1
AEN	XM_047432947.1	c.-65+3000C>T		intron_variant			XP_047288903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIR7-2	ENST00000384970.1	n.18C>T		non_coding_transcript_exon_variant	1/1	6
MIR3529	ENST00000637713.1	n.*5G>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 752 AN: 152072 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00661 AC: 1520 AN: 230030 Hom.: 19 AF XY: 0.00731 AC XY: 912 AN XY: 124770

Gnomad AFR exome AF: 0.000349

Gnomad AMR exome AF: 0.00176

Gnomad ASJ exome AF: 0.000629

Gnomad EAS exome AF: 0.000123

Gnomad SAS exome AF: 0.0129

Gnomad FIN exome AF: 0.0352

Gnomad NFE exome AF: 0.00310

Gnomad OTH exome AF: 0.00873

GnomAD4 exome AF: 0.00735 AC: 2698 AN: 367182 Hom.: 48 Cov.: 0 AF XY: 0.00782 AC XY: 1638 AN XY: 209456

Gnomad4 AFR exome AF: 0.000624

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.000704

Gnomad4 EAS exome AF: 0.0000861

Gnomad4 SAS exome AF: 0.0138

Gnomad4 FIN exome AF: 0.0349

Gnomad4 NFE exome AF: 0.00255

Gnomad4 OTH exome AF: 0.00826

GnomAD4 genome AF: 0.00493 AC: 750 AN: 152190 Hom.: 5 Cov.: 32 AF XY: 0.00671 AC XY: 499 AN XY: 74392

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.00406

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00293 Hom.: 2

Bravo AF: 0.00194

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41276930; hg19: chr15-89155073;