11-46539130-C-T

Position:

• chr11-46539130-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

AMBRA1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMBRA1	NM_001387011.1	c.2072+2815G>A		intron_variant		ENST00000683756.1	NP_001373940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMBRA1	ENST00000683756.1	c.2072+2815G>A		intron_variant			NM_001387011.1	ENSP00000508322.1

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

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0593

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.225

Alfa AF: 0.181 Hom.: 3726

Bravo AF: 0.272

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.83
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs11819869; hg19: chr11-46560680;