15-33946603-C-T

Position:

• chr15-33946603-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020371.3(AVEN):​c.445+56429G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,950 control chromosomes in the GnomAD database, including 37,039 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 0.66 (37039 hom., cov: 31)
• Consequence: AVEN NM_020371.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.292

Genes affected

AVEN (HGNC:13509): (apoptosis and caspase activation inhibitor) Involved in negative regulation of apoptotic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.82 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVEN	NM_020371.3	c.445+56429G>A		intron_variant		ENST00000306730.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVEN	ENST00000306730.8	c.445+56429G>A		intron_variant		1	NM_020371.3	P1
AVEN	ENST00000675287.1	n.1815+56429G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99641 AN: 151832 Hom.: 37047 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.887

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.656 AC: 99650 AN: 151950 Hom.: 37039 Cov.: 31 AF XY: 0.656 AC XY: 48714 AN XY: 74272

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.836

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.825

Gnomad4 OTH AF: 0.717

Alfa AF: 0.795 Hom.: 65208

Bravo AF: 0.639

Asia WGS AF: 0.707 AC: 2457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs525243; hg19: chr15-34238804;