12-8606214-G-A

Variant names:

• chr12-8606214-G-A
• rs2580874
• NM_020661.4:c.156+651C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020661.4(AICDA):​c.156+651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,094 control chromosomes in the GnomAD database, including 24,114 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (24114 hom., cov: 32)
• Consequence: AICDA NM_020661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 8 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020661.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AICDA	NM_020661.4	MANE Select	c.156+651C>T		intron	N/A	NP_065712.1
	AICDA	NM_001330343.2		c.156+651C>T		intron	N/A	NP_001317272.1
	AICDA	NM_001410970.1		c.156+651C>T		intron	N/A	NP_001397899.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AICDA	ENST00000229335.11	TSL:1 MANE Select	c.156+651C>T		intron	N/A	ENSP00000229335.6
	AICDA	ENST00000543081.6	TSL:1	c.156+651C>T		intron	N/A	ENSP00000439103.2
	AICDA	ENST00000544516.6	TSL:1	c.156+651C>T		intron	N/A	ENSP00000439538.2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83150 AN: 151976 Hom.: 24073 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.492

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.547 AC: 83247 AN: 152094 Hom.: 24114 Cov.: 32 AF XY: 0.554 AC XY: 41205 AN XY: 74336

African (AFR) AF: 0.711 AC: 29512 AN: 41486

American (AMR) AF: 0.502 AC: 7671 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1289 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4232 AN: 5160

South Asian (SAS) AF: 0.589 AC: 2837 AN: 4816

European-Finnish (FIN) AF: 0.546 AC: 5769 AN: 10574

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30340 AN: 67988

Other (OTH) AF: 0.497 AC: 1051 AN: 2114

Alfa AF: 0.474 Hom.: 55849

Bravo AF: 0.550

Asia WGS AF: 0.686 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.93
DANN	Benign	0.67
PhyloP100		-0.0080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2580874; hg19: chr12-8758810;