12-8602830-T-TC

Position:

• chr12-8602830-T-TC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_020661.4(AICDA):​c.*1453_*1454insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 119,618 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.013 (18 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AICDA NM_020661.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.39

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AICDA	NM_020661.4	c.*1453_*1454insG		3_prime_UTR_variant	5/5	ENST00000229335.11	NP_065712.1
AICDA	NM_001330343.2	c.*1453_*1454insG		3_prime_UTR_variant	5/5		NP_001317272.1
AICDA	NM_001410970.1	c.*1496_*1497insG		3_prime_UTR_variant	4/4		NP_001397899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AICDA	ENST00000229335.11	c.*1453_*1454insG		3_prime_UTR_variant	5/5	1	NM_020661.4	ENSP00000229335	P1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1537 AN: 119632 Hom.: 18 Cov.: 31

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000425

Gnomad SAS AF: 0.000485

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000277

Gnomad OTH AF: 0.00733

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 134 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 98

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0128 AC: 1537 AN: 119618 Hom.: 18 Cov.: 31 AF XY: 0.0127 AC XY: 739 AN XY: 58298

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000426

Gnomad4 SAS AF: 0.000487

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000277

Gnomad4 OTH AF: 0.00729

Alfa AF: 0.0114 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyperimmunoglobulin M syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs201738977; hg19: chr12-8755426;