11-46539130-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001387011.1(AMBRA1):​c.2072+2815G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,686 control chromosomes in the GnomAD database, including 7,097 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 0.26 (7097 hom., 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

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>A		intron	N/A	NP_001373940.1
	AMBRA1	NM_001267782.2		c.1802+2815G>A		intron	N/A	NP_001254711.1
	AMBRA1	NM_001367468.1		c.2072+2815G>A		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>A		intron	N/A	ENSP00000508322.1
	AMBRA1	ENST00000534300.5	TSL:1	c.2072+2815G>A		intron	N/A	ENSP00000431926.1
	AMBRA1	ENST00000314845.7	TSL:1	c.1802+2815G>A		intron	N/A	ENSP00000318313.3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39122 AN: 151568 Hom.: 7072 Cov.: 31

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.258 AC: 39192 AN: 151686 Hom.: 7097 Cov.: 31 AF XY: 0.251 AC XY: 18567 AN XY: 74112

African (AFR) AF: 0.518 AC: 21384 AN: 41280

American (AMR) AF: 0.151 AC: 2291 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3468

East Asian (EAS) AF: 0.0593 AC: 307 AN: 5176

South Asian (SAS) AF: 0.152 AC: 730 AN: 4808

European-Finnish (FIN) AF: 0.120 AC: 1268 AN: 10524

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.174 AC: 11809 AN: 67920

Other (OTH) AF: 0.225 AC: 475 AN: 2108

Alfa AF: 0.191 Hom.: 5511

Bravo AF: 0.272

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.83
DANN	Benign	0.37
PhyloP100		-0.36
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: rs11819869; hg19: chr11-46560680;