12-116576326-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001085481.3(MAP1LC3B2):c.*12dup variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,600,402 control chromosomes in the GnomAD database, including 56,546 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5036 hom., cov: 22)
  • Exomes 𝑓: 0.26 (51510 hom.)
• Consequence: MAP1LC3B2 NM_001085481.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0610

Genes affected

MAP1LC3B2 (HGNC:34390): (microtubule associated protein 1 light chain 3 beta 2) Predicted to enable microtubule binding activity and ubiquitin protein ligase binding activity. Predicted to be involved in autophagy of mitochondrion; cellular response to nitrogen starvation; and macroautophagy. Located in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-116576326-G-GA is Benign according to our data. Variant chr12-116576326-G-GA is described in ClinVar as [Benign]. Clinvar id is 2688190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP1LC3B2	NM_001085481.3	c.*12dup		3_prime_UTR_variant	2/2	ENST00000556529.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP1LC3B2	ENST00000556529.4	c.*12dup		3_prime_UTR_variant	2/2	3	NM_001085481.3	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37519 AN: 151182 Hom.: 5034 Cov.: 22

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.270

GnomAD3 exomes AF: 0.257 AC: 58091 AN: 225700 Hom.: 9383 AF XY: 0.266 AC XY: 32595 AN XY: 122478

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.140

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.491

Gnomad SAS exome AF: 0.281

Gnomad FIN exome AF: 0.276

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.261 AC: 378584 AN: 1449102 Hom.: 51510 Cov.: 38 AF XY: 0.265 AC XY: 190658 AN XY: 720608

Gnomad4 AFR exome AF: 0.170

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.337

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.302

Gnomad4 FIN exome AF: 0.283

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.277

GnomAD4 genome AF: 0.248 AC: 37531 AN: 151300 Hom.: 5036 Cov.: 22 AF XY: 0.250 AC XY: 18485 AN XY: 73904

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.273

Alfa AF: 0.266 Hom.: 1073

Bravo AF: 0.238

Asia WGS AF: 0.337 AC: 1171 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 38% of patients studied by a panel of primary immunodeficiencies. Number of patients: 36. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

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: rs55717114; hg19: chr12-117014131;