12-116575925-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001085481.3(MAP1LC3B2):c.-18G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.672 in 1,613,678 control chromosomes in the GnomAD database, including 373,536 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (30499 hom., cov: 33)
  • Exomes 𝑓: 0.68 (343037 hom.)
• Consequence: MAP1LC3B2 NM_001085481.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.642

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-116575925-G-C is Benign according to our data. Variant chr12-116575925-G-C is described in ClinVar as [Benign]. Clinvar id is 2688029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAP1LC3B2	NM_001085481.3	c.-18G>C		5_prime_UTR_variant	2/2	ENST00000556529.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAP1LC3B2	ENST00000556529.4	c.-18G>C		5_prime_UTR_variant	2/2	3	NM_001085481.3	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94720 AN: 151876 Hom.: 30502 Cov.: 33

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.624

GnomAD3 exomes AF: 0.595 AC: 149167 AN: 250672 Hom.: 47415 AF XY: 0.605 AC XY: 82032 AN XY: 135684

Gnomad AFR exome AF: 0.574

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.622

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.561

Gnomad FIN exome AF: 0.646

Gnomad NFE exome AF: 0.711

Gnomad OTH exome AF: 0.637

GnomAD4 exome AF: 0.678 AC: 990438 AN: 1461682 Hom.: 343037 Cov.: 70 AF XY: 0.675 AC XY: 490588 AN XY: 727154

Gnomad4 AFR exome AF: 0.573

Gnomad4 AMR exome AF: 0.392

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.651

Gnomad4 NFE exome AF: 0.719

Gnomad4 OTH exome AF: 0.651

GnomAD4 genome AF: 0.623 AC: 94751 AN: 151996 Hom.: 30499 Cov.: 33 AF XY: 0.614 AC XY: 45616 AN XY: 74288

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.546

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.624

Alfa AF: 0.593 Hom.: 3430

Bravo AF: 0.609

Asia WGS AF: 0.444 AC: 1547 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 67% of patients studied by a panel of primary immunodeficiencies. Number of patients: 64. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.54
Dann	Benign	0.73

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: rs7303998; hg19: chr12-117013730; COSMIC: COSV61010015;