17-42811886-G-A

Variant names:

• chr17-42811886-G-A
• rs10512488
• NM_001313998.2:c.1042-89C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 29 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
BECN1	NM_001313998.2	c.1042-89C>T		intron_variant	Intron 10 of 11	ENST00000590099.6	NP_001300927.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BECN1	ENST00000590099.6	c.1042-89C>T		intron_variant	Intron 10 of 11	1	NM_001313998.2	ENSP00000465364.1

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

African (AFR) AF: 0.0348 AC: 1025 AN: 29454

American (AMR) AF: 0.188 AC: 5882 AN: 31294

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 4307 AN: 20598

East Asian (EAS) AF: 0.0202 AC: 782 AN: 38656

South Asian (SAS) AF: 0.134 AC: 9479 AN: 70826

European-Finnish (FIN) AF: 0.252 AC: 12671 AN: 50284

Middle Eastern (MID) AF: 0.147 AC: 650 AN: 4426

European-Non Finnish (NFE) AF: 0.252 AC: 258646 AN: 1027022

Other (OTH) AF: 0.208 AC: 11484 AN: 55286

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

African (AFR) AF: 0.0433 AC: 1798 AN: 41556

American (AMR) AF: 0.173 AC: 2649 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3466

East Asian (EAS) AF: 0.0316 AC: 164 AN: 5186

South Asian (SAS) AF: 0.124 AC: 599 AN: 4822

European-Finnish (FIN) AF: 0.256 AC: 2706 AN: 10566

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17168 AN: 67968

Other (OTH) AF: 0.157 AC: 332 AN: 2114

Alfa AF: 0.235 Hom.: 7655

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
PhyloP100		-0.13
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: rs10512488; hg19: chr17-40963904;