15-33946603-C-T

Variant names:

• chr15-33946603-C-T
• rs525243
• NM_020371.3:c.445+56429G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020371.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVEN	NM_020371.3	MANE Select	c.445+56429G>A		intron	N/A	NP_065104.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AVEN	ENST00000306730.8	TSL:1 MANE Select	c.445+56429G>A		intron	N/A	ENSP00000306822.3
	AVEN	ENST00000964283.1		c.446-40811G>A		intron	N/A	ENSP00000634342.1
	AVEN	ENST00000964282.1		c.445+56429G>A		intron	N/A	ENSP00000634341.1

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

African (AFR) AF: 0.276 AC: 11438 AN: 41386

American (AMR) AF: 0.746 AC: 11394 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2902 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4017 AN: 5152

South Asian (SAS) AF: 0.697 AC: 3358 AN: 4820

European-Finnish (FIN) AF: 0.749 AC: 7913 AN: 10570

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56103 AN: 67974

Other (OTH) AF: 0.717 AC: 1509 AN: 2106

Alfa AF: 0.779 Hom.: 79713

Bravo AF: 0.639

Asia WGS AF: 0.707 AC: 2457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.54
PhyloP100		-0.29
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: rs525243; hg19: chr15-34238804;