rs10519897

Variant names:

• chr15-33958911-A-C
• rs10519897
• NM_020371.3:c.445+44121T>G

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+44121T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 152,144 control chromosomes in the GnomAD database, including 212 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 0.023 (212 hom., cov: 32)
• Consequence: AVEN NM_020371.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.633
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AVEN	NM_020371.3	c.445+44121T>G		intron_variant	Intron 2 of 5	ENST00000306730.8	NP_065104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AVEN	ENST00000306730.8	c.445+44121T>G		intron_variant	Intron 2 of 5	1	NM_020371.3	ENSP00000306822.3
AVEN	ENST00000675287.1	n.1815+44121T>G		intron_variant	Intron 6 of 11

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3555 AN: 152024 Hom.: 208 Cov.: 32

Gnomad AFR AF: 0.00500

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0230

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

GnomAD4 genome AF: 0.0234 AC: 3566 AN: 152144 Hom.: 212 Cov.: 32 AF XY: 0.0250 AC XY: 1862 AN XY: 74384

African (AFR) AF: 0.00499 AC: 207 AN: 41500

American (AMR) AF: 0.135 AC: 2065 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5170

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4818

European-Finnish (FIN) AF: 0.0126 AC: 134 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1027 AN: 67992

Other (OTH) AF: 0.0228 AC: 48 AN: 2106

Alfa AF: 0.0214 Hom.: 51

Bravo AF: 0.0335

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.81
PhyloP100		0.63
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: rs10519897; hg19: chr15-34251112;