rs10512488

chr17-42811886-G-A

Variant summary

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

The NM_001313998.2(BECN1):c.1042-89C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,480,016 control chromosomes in the GnomAD database, including 40,723 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 0.17 (3065 hom., cov: 32)
  • Exomes 𝑓: 0.23 (37658 hom.)
• Consequence: BECN1 NM_001313998.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

Genes affected

BECN1 (HGNC:1034): (beclin 1) This gene encodes a protein that regulates autophagy, a catabolic process of degradation induced by starvation. The encoded protein is a component of the phosphatidylinositol-3-kinase (PI3K) complex which mediates vesicle-trafficking processes. This protein is thought to play a role in multiple cellular processes, including tumorigenesis, neurodegeneration and apoptosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BECN1	NM_001313998.2	c.1042-89C>T		intron_variant		ENST00000590099.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BECN1	ENST00000590099.6	c.1042-89C>T		intron_variant		1	NM_001313998.2	P1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26519 AN: 152052 Hom.: 3068 Cov.: 32

Gnomad AFR AF: 0.0435

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.230 AC: 304926 AN: 1327846 Hom.: 37658 Cov.: 20 AF XY: 0.227 AC XY: 149205 AN XY: 656332

Gnomad4 AFR exome AF: 0.0348

Gnomad4 AMR exome AF: 0.188

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.0202

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome AF: 0.174 AC: 26503 AN: 152170 Hom.: 3065 Cov.: 32 AF XY: 0.172 AC XY: 12777 AN XY: 74402

Gnomad4 AFR AF: 0.0433

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.0316

Gnomad4 SAS AF: 0.124

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.157

Alfa AF: 0.229 Hom.: 2546

Bravo AF: 0.163

Asia WGS AF: 0.0690 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.40
Dann	Benign	0.32

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: rs10512488; hg19: chr17-40963904;