rs10519888

Positions:

• chr15-33875915-C-G

Variant summary

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

The NM_020371.3(AVEN):​c.516+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.025 in 1,611,950 control chromosomes in the GnomAD database, including 3,924 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 0.053 (665 hom., cov: 32)
  • Exomes 𝑓: 0.022 (3259 hom.)
• Consequence: AVEN NM_020371.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AVEN	NM_020371.3	c.516+10G>C		intron_variant		ENST00000306730.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AVEN	ENST00000306730.8	c.516+10G>C		intron_variant		1	NM_020371.3	P1
AVEN	ENST00000560649.1	c.70+10G>C		intron_variant, NMD_transcript_variant		5
AVEN	ENST00000558136.1	n.274+10G>C		intron_variant, non_coding_transcript_variant		5
AVEN	ENST00000675287.1	n.1886+10G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8114 AN: 152064 Hom.: 668 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.0363

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00720

Gnomad OTH AF: 0.0502

GnomAD3 exomes AF: 0.0470 AC: 11793 AN: 251162 Hom.: 1512 AF XY: 0.0431 AC XY: 5856 AN XY: 135766

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0191

Gnomad ASJ exome AF: 0.0401

Gnomad EAS exome AF: 0.381

Gnomad SAS exome AF: 0.0205

Gnomad FIN exome AF: 0.00988

Gnomad NFE exome AF: 0.00698

Gnomad OTH exome AF: 0.0302

GnomAD4 exome AF: 0.0220 AC: 32136 AN: 1459768 Hom.: 3259 Cov.: 29 AF XY: 0.0217 AC XY: 15740 AN XY: 726364

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.0197

Gnomad4 ASJ exome AF: 0.0391

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.0230

Gnomad4 FIN exome AF: 0.00912

Gnomad4 NFE exome AF: 0.00614

Gnomad4 OTH exome AF: 0.0387

GnomAD4 genome AF: 0.0534 AC: 8121 AN: 152182 Hom.: 665 Cov.: 32 AF XY: 0.0540 AC XY: 4017 AN XY: 74412

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.373

Gnomad4 SAS AF: 0.0363

Gnomad4 FIN AF: 0.00970

Gnomad4 NFE AF: 0.00720

Gnomad4 OTH AF: 0.0516

Alfa AF: 0.0300 Hom.: 44

Bravo AF: 0.0609

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.34
DANN	Benign	0.56

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: rs10519888; hg19: chr15-34168116; COSMIC: COSV60733138;