rs11552193

Variant names:

• chr17-42810222-C-T
• rs11552193
• NM_001313998.2:c.*538G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003766.5(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. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BECN1 NM_003766.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.119
• Publications: 2 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]

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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003766.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BECN1	NM_001313998.2	MANE Select	c.*538G>A		3_prime_UTR	Exon 12 of 12	NP_001300927.1
	CNTD1	NM_173478.3	MANE Select	c.*687C>T		3_prime_UTR	Exon 7 of 7	NP_775749.2
	BECN1	NM_003766.5		c.*538G>A		3_prime_UTR	Exon 12 of 12	NP_003757.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BECN1	ENST00000590099.6	TSL:1 MANE Select	c.*538G>A		3_prime_UTR	Exon 12 of 12	ENSP00000465364.1
	CNTD1	ENST00000588408.6	TSL:1 MANE Select	c.*687C>T		3_prime_UTR	Exon 7 of 7	ENSP00000465204.1
	BECN1	ENST00000361523.8	TSL:1	c.*538G>A		3_prime_UTR	Exon 12 of 12	ENSP00000355231.3

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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 144

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 418

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 198

Other (OTH) AF: 0.00 AC: 0 AN: 10

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

African (AFR) AF: 0.000866 AC: 36 AN: 41550

American (AMR) AF: 0.00144 AC: 22 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00296 AC: 201 AN: 68010

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00187 Hom.: 0

Bravo AF: 0.00188

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.78
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs11552193; hg19: chr17-40962240;