rs2028373

Positions:

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

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]

AICDA links:

Genome browser will be placed here

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
AICDA	NM_020661.4 linkuse as main transcript	c.465C>T	p.His155=	synonymous_variant	4/5	ENST00000229335.11
AICDA	NM_001330343.2 linkuse as main transcript	c.435C>T	p.His145=	synonymous_variant	4/5
AICDA	NM_001410970.1 linkuse as main transcript	c.427+330C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AICDA	ENST00000229335.11 linkuse as main transcript	c.465C>T	p.His155=	synonymous_variant	4/5	1	NM_020661.4	P1	Q9GZX7-1

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

80823

AN:

149028

Hom.:

23245

Cov.:

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.:

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.:

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 submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 10, 2014	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This 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 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 86% of patients studied by a panel of primary immunodeficiencies. Number of patients: 82. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 28, 2015	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over