chr12-8604885-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_020661.4(AICDA):​c.465C>T​(p.His155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 1,609,966 control chromosomes in the GnomAD database, including 312,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23255 hom., cov: 26)
Exomes 𝑓: 0.63 ( 289306 hom. )

Consequence

AICDA
NM_020661.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11O:1

Conservation

PhyloP100: -0.164
Variant links:
Genes affected
AICDA (HGNC:13203): (activation induced cytidine deaminase) This gene encodes a RNA-editing deaminase that is a member of the cytidine deaminase family. AICDA is specifically expressed and active in germinal center-like B cells. In the germinal center, AICDA is involved in somatic hypermutation, gene conversion, and class-switch recombination of immunoglobulin genes. An epigenetic role in neoplastic transformation and lymphoma progression has been experimentally ascribed to AICDA using mouse models. Defects in this gene are the cause of autosomal recessive hyper-IgM immunodeficiency syndrome type 2 (HIGM2). [provided by RefSeq, Jul 2020]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 12-8604885-G-A is Benign according to our data. Variant chr12-8604885-G-A is described in ClinVar as [Benign]. Clinvar id is 261353.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-8604885-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.164 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AICDANM_020661.4 linkuse as main transcriptc.465C>T p.His155= synonymous_variant 4/5 ENST00000229335.11
AICDANM_001330343.2 linkuse as main transcriptc.435C>T p.His145= synonymous_variant 4/5
AICDANM_001410970.1 linkuse as main transcriptc.427+330C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AICDAENST00000229335.11 linkuse as main transcriptc.465C>T p.His155= synonymous_variant 4/51 NM_020661.4 P1Q9GZX7-1

Frequencies

GnomAD3 genomes
AF:
0.542
AC:
80823
AN:
149028
Hom.:
23245
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.319
Gnomad AMI
AF:
0.649
Gnomad AMR
AF:
0.626
Gnomad ASJ
AF:
0.601
Gnomad EAS
AF:
0.484
Gnomad SAS
AF:
0.544
Gnomad FIN
AF:
0.616
Gnomad MID
AF:
0.561
Gnomad NFE
AF:
0.646
Gnomad OTH
AF:
0.557
GnomAD3 exomes
AF:
0.597
AC:
148184
AN:
248232
Hom.:
45374
AF XY:
0.598
AC XY:
80672
AN XY:
134922
show subpopulations
Gnomad AFR exome
AF:
0.312
Gnomad AMR exome
AF:
0.665
Gnomad ASJ exome
AF:
0.601
Gnomad EAS exome
AF:
0.503
Gnomad SAS exome
AF:
0.542
Gnomad FIN exome
AF:
0.611
Gnomad NFE exome
AF:
0.641
Gnomad OTH exome
AF:
0.604
GnomAD4 exome
AF:
0.625
AC:
913525
AN:
1460840
Hom.:
289306
Cov.:
66
AF XY:
0.625
AC XY:
453963
AN XY:
726714
show subpopulations
Gnomad4 AFR exome
AF:
0.302
Gnomad4 AMR exome
AF:
0.663
Gnomad4 ASJ exome
AF:
0.594
Gnomad4 EAS exome
AF:
0.469
Gnomad4 SAS exome
AF:
0.551
Gnomad4 FIN exome
AF:
0.610
Gnomad4 NFE exome
AF:
0.648
Gnomad4 OTH exome
AF:
0.602
GnomAD4 genome
AF:
0.542
AC:
80853
AN:
149126
Hom.:
23255
Cov.:
26
AF XY:
0.543
AC XY:
39353
AN XY:
72528
show subpopulations
Gnomad4 AFR
AF:
0.319
Gnomad4 AMR
AF:
0.626
Gnomad4 ASJ
AF:
0.601
Gnomad4 EAS
AF:
0.485
Gnomad4 SAS
AF:
0.545
Gnomad4 FIN
AF:
0.616
Gnomad4 NFE
AF:
0.646
Gnomad4 OTH
AF:
0.555
Alfa
AF:
0.618
Hom.:
71819
Bravo
AF:
0.533
Asia WGS
AF:
0.457
AC:
1590
AN:
3476
EpiCase
AF:
0.644
EpiControl
AF:
0.639

ClinVar

Significance: Benign
Submissions summary: Benign:11Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Hyper-IgM syndrome type 2 Benign:5
Benign, criteria provided, single submitterclinical testingGenome Diagnostics Laboratory, University Medical Center UtrechtOct 10, 2014- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not specified Benign:4
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This variant is classified as Benign based on local population frequency. This variant was detected in 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Sep 28, 2015- -
not provided Benign:2Other:1
Benign, criteria provided, single submitterclinical testingGeneDxMar 03, 2015- -
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not provided, no classification providedphenotyping onlyGenomeConnect, ClinGen-Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
3.0
DANN
Benign
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs2028373; hg19: chr12-8757481; COSMIC: COSV57564585; API