11-46539130-C-A

Variant names:

• chr11-46539130-C-A
• rs11819869
• NM_001387011.1:c.2072+2815G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387011.1(AMBRA1):​c.2072+2815G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: AMBRA1 NM_001387011.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 18 publications found

Genes affected

AMBRA1 (HGNC:25990): (autophagy and beclin 1 regulator 1) Enables GTPase binding activity and ubiquitin protein ligase binding activity. Involved in macroautophagy; positive regulation of phosphatidylinositol 3-kinase activity; and response to mitochondrial depolarisation. Located in cytosol. Colocalizes with mitochondrion. Biomarker of multiple system atrophy. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387011.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMBRA1	NM_001387011.1	MANE Select	c.2072+2815G>T		intron	N/A	NP_001373940.1
	AMBRA1	NM_001267782.2		c.1802+2815G>T		intron	N/A	NP_001254711.1
	AMBRA1	NM_001367468.1		c.2072+2815G>T		intron	N/A	NP_001354397.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMBRA1	ENST00000683756.1	MANE Select	c.2072+2815G>T		intron	N/A	ENSP00000508322.1
	AMBRA1	ENST00000534300.5	TSL:1	c.2072+2815G>T		intron	N/A	ENSP00000431926.1
	AMBRA1	ENST00000314845.7	TSL:1	c.1802+2815G>T		intron	N/A	ENSP00000318313.3

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 5511

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.29
PhyloP100		-0.36

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: rs11819869; hg19: chr11-46560680;