11-46521974-C-T

Position:

• chr11-46521974-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.2073-9161G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,096 control chromosomes in the GnomAD database, including 18,496 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 0.43 (18496 hom., cov: 33)
• Consequence: AMBRA1 NM_001387011.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AMBRA1	NM_001387011.1	c.2073-9161G>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.2073-9161G>A		intron_variant			NM_001387011.1	ENSP00000508322.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64732 AN: 151978 Hom.: 18435 Cov.: 33

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.426 AC: 64847 AN: 152096 Hom.: 18496 Cov.: 33 AF XY: 0.416 AC XY: 30911 AN XY: 74368

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.283

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.400

Alfa AF: 0.328 Hom.: 4729

Bravo AF: 0.449

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.9
DANN	Benign	0.78

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: rs11038910; hg19: chr11-46543524;