rs10519897

Positions:

• chr15-33958911-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	UniProt
AVEN	NM_020371.3	c.445+44121T>G		intron_variant		ENST00000306730.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVEN	ENST00000306730.8	c.445+44121T>G		intron_variant		1	NM_020371.3	P1
AVEN	ENST00000675287.1	n.1815+44121T>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.00499

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0228

Alfa AF: 0.0188 Hom.: 14

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

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: rs10519897; hg19: chr15-34251112;