rs2580874

chr12-8606214-G-Achr12-8606214-G-Cchr12-8606214-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AICDA	NM_020661.4	c.156+651C>T		intron_variant		ENST00000229335.11
AICDA	NM_001330343.2	c.156+651C>T		intron_variant
AICDA	NM_001410970.1	c.156+651C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AICDA	ENST00000229335.11	c.156+651C>T		intron_variant		1	NM_020661.4	P1

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

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.589

Gnomad4 FIN AF: 0.546

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.497

Alfa AF: 0.446 Hom.: 20178

Bravo AF: 0.550

Asia WGS AF: 0.686 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.93
Dann	Benign	0.67

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

Other links and lift over

dbSNP: rs2580874; hg19: chr12-8758810;