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GeneBe

12-116575951-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001085481.3(MAP1LC3B2):c.9G>A(p.Ser3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,614,158 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 10 hom., cov: 32)
Exomes 𝑓: 0.013 ( 165 hom. )

Consequence

MAP1LC3B2
NM_001085481.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.202
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-116575951-G-A is Benign according to our data. Variant chr12-116575951-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2643372.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.202 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0135 (19724/1461892) while in subpopulation MID AF= 0.0187 (108/5768). AF 95% confidence interval is 0.0159. There are 165 homozygotes in gnomad4_exome. There are 9594 alleles in male gnomad4_exome subpopulation. Median coverage is 39. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 10 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MAP1LC3B2NM_001085481.3 linkuse as main transcriptc.9G>A p.Ser3= synonymous_variant 2/2 ENST00000556529.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MAP1LC3B2ENST00000556529.4 linkuse as main transcriptc.9G>A p.Ser3= synonymous_variant 2/23 NM_001085481.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00947
AC:
1441
AN:
152148
Hom.:
10
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00270
Gnomad AMI
AF:
0.0132
Gnomad AMR
AF:
0.0103
Gnomad ASJ
AF:
0.0107
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00352
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.0253
Gnomad NFE
AF:
0.0153
Gnomad OTH
AF:
0.0192
GnomAD3 exomes
AF:
0.00944
AC:
2373
AN:
251430
Hom.:
18
AF XY:
0.00970
AC XY:
1318
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00240
Gnomad AMR exome
AF:
0.00766
Gnomad ASJ exome
AF:
0.0123
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00500
Gnomad FIN exome
AF:
0.00240
Gnomad NFE exome
AF:
0.0146
Gnomad OTH exome
AF:
0.0121
GnomAD4 exome
AF:
0.0135
AC:
19724
AN:
1461892
Hom.:
165
Cov.:
39
AF XY:
0.0132
AC XY:
9594
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00227
Gnomad4 AMR exome
AF:
0.00816
Gnomad4 ASJ exome
AF:
0.0125
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00516
Gnomad4 FIN exome
AF:
0.00298
Gnomad4 NFE exome
AF:
0.0156
Gnomad4 OTH exome
AF:
0.0149
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00946
AC:
1440
AN:
152266
Hom.:
10
Cov.:
32
AF XY:
0.00901
AC XY:
671
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00270
Gnomad4 AMR
AF:
0.0103
Gnomad4 ASJ
AF:
0.0107
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00352
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.0153
Gnomad4 OTH
AF:
0.0190
Alfa
AF:
0.00954
Hom.:
5
Bravo
AF:
0.0101
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJun 01, 2022MAP1LC3B2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
Cadd
Benign
6.2
Dann
Benign
0.74

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147123589; hg19: chr12-117013756; COSMIC: COSV100186542; API