rs11552193

Positions:

• chr17-42810222-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001313998.2(BECN1):​c.*538G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 152,250 control chromosomes in the GnomAD database, including 1 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 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BECN1 NM_001313998.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119

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]

CNTD1 (HGNC:26847): (cyclin N-terminal domain containing 1) Predicted to be involved in reciprocal meiotic recombination. Predicted to act upstream of or within spermatogenesis. Predicted to be active in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

CNTD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BS2: High AC in GnomAd4 at 276 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BECN1	NM_001313998.2	c.*538G>A		3_prime_UTR_variant	12/12	ENST00000590099.6	NP_001300927.1
CNTD1	NM_173478.3	c.*687C>T		3_prime_UTR_variant	7/7	ENST00000588408.6	NP_775749.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BECN1	ENST00000590099	c.*538G>A		3_prime_UTR_variant	12/12	1	NM_001313998.2	ENSP00000465364.1
CNTD1	ENST00000588408.6	c.*687C>T		3_prime_UTR_variant	7/7	1	NM_173478.3	ENSP00000465204.1

Frequencies

GnomAD3 genomes AF: 0.00181 AC: 276 AN: 152132 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00296

Gnomad OTH AF: 0.00191

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 788 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 456

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00181 AC: 276 AN: 152250 Hom.: 1 Cov.: 32 AF XY: 0.00165 AC XY: 123 AN XY: 74466

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00296

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00187 Hom.: 0

Bravo AF: 0.00188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11552193; hg19: chr17-40962240;