12-8606849-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020661.4(AICDA):c.156+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,613,040 control chromosomes in the GnomAD database, including 201,129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.56 ( 25191 hom., cov: 32)

Exomes 𝑓: 0.48 ( 175938 hom. )

Consequence

AICDA
NM_020661.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.291

Publications

17 publications found

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]

AICDA Gene-Disease associations (from GenCC):

hyper-IgM syndrome type 2
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

AICDA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-8606849-C-T is Benign according to our data. Variant chr12-8606849-C-T is described in ClinVar as Benign. ClinVar VariationId is 261352.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AICDA	NM_020661.4 link	c.156+16G>A	intron_variant	Intron 2 of 4	ENST00000229335.11	NP_065712.1	Q9GZX7-1Q546Y9Q7Z599
AICDA	NM_001330343.2 link	c.156+16G>A	intron_variant	Intron 2 of 4		NP_001317272.1	Q9GZX7-2Q7Z599
AICDA	NM_001410970.1 link	c.156+16G>A	intron_variant	Intron 2 of 3		NP_001397899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AICDA	ENST00000229335.11 link	c.156+16G>A		intron_variant	Intron 2 of 4	1	NM_020661.4	ENSP00000229335.6		Q9GZX7-1

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84882

AN:

151946

Hom.:

25146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.740

Gnomad AMI

AF:

0.499

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.810

Gnomad SAS

AF:

0.588

Gnomad FIN

AF:

0.563

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.494

GnomAD2 exomes

AF:

0.526

AC:

130961

AN:

249030

AF XY:

0.518

show subpopulations

Gnomad AFR exome

AF:

0.744

Gnomad AMR exome

AF:

0.509

Gnomad ASJ exome

AF:

0.375

Gnomad EAS exome

AF:

0.793

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.475

GnomAD4 exome

AF:

0.483

AC:

704926

AN:

1460976

Hom.:

175938

Cov.:

AF XY:

0.483

AC XY:

351096

AN XY:

726854

show subpopulations

African (AFR)

AF:

0.745

AC:

24944

AN:

33470

American (AMR)

AF:

0.506

AC:

22637

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

9981

AN:

26126

East Asian (EAS)

AF:

0.838

AC:

33250

AN:

39690

South Asian (SAS)

AF:

0.564

AC:

48646

AN:

86216

European-Finnish (FIN)

AF:

0.567

AC:

30263

AN:

53338

Middle Eastern (MID)

AF:

0.408

AC:

2354

AN:

5766

European-Non Finnish (NFE)

AF:

0.453

AC:

503129

AN:

1111306

Other (OTH)

AF:

0.492

AC:

29722

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

17863

35727

53590

71454

89317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15346

30692

46038

61384

76730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.559

AC:

84987

AN:

152064

Hom.:

25191

Cov.:

AF XY:

0.566

AC XY:

42087

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.739

AC:

30680

AN:

41490

American (AMR)

AF:

0.497

AC:

7593

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.380

AC:

1315

AN:

3464

East Asian (EAS)

AF:

0.811

AC:

4199

AN:

5178

South Asian (SAS)

AF:

0.588

AC:

2834

AN:

4820

European-Finnish (FIN)

AF:

0.563

AC:

5946

AN:

10558

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.453

AC:

30793

AN:

67960

Other (OTH)

AF:

0.500

AC:

1054

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1820

3640

5461

7281

9101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.498

Hom.:

6379

Bravo

AF:

0.559

Asia WGS

AF:

0.681

AC:

2364

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hyper-IgM syndrome type 2

Benign:4

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant 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 -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 66% of patients studied by a panel of primary immunodeficiencies. Number of patients: 63. Only high quality variants are reported. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.69

(source)

DANN

Benign

0.56

PhyloP100

0.29

PromoterAI

-0.0074

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over