11-46521974-C-T

Variant names:

• chr11-46521974-C-T
• rs11038910
• NM_001387011.1:c.2073-9161G>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.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
• Publications: 4 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=-0.82).
• 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 rank	MANE	Protein	UniProt
AMBRA1	NM_001387011.1	c.2073-9161G>A		intron_variant	Intron 7 of 17	ENST00000683756.1	NP_001373940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMBRA1	ENST00000683756.1	c.2073-9161G>A		intron_variant	Intron 7 of 17		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

African (AFR) AF: 0.814 AC: 33795 AN: 41518

American (AMR) AF: 0.283 AC: 4323 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3470

East Asian (EAS) AF: 0.139 AC: 719 AN: 5170

South Asian (SAS) AF: 0.327 AC: 1580 AN: 4826

European-Finnish (FIN) AF: 0.165 AC: 1747 AN: 10580

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.296 AC: 20094 AN: 67944

Other (OTH) AF: 0.400 AC: 844 AN: 2112

Alfa AF: 0.327 Hom.: 5186

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
PhyloP100		-0.029
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: rs11038910; hg19: chr11-46543524;