12-8604926-CAAAAAAAAA-CAAAAAAAA

Variant names:

• chr12-8604926-CA-C
• rs5796316
• NM_020661.4:c.428-5delT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_020661.4(AICDA):​c.428-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00144 in 1,372,598 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (1 hom.)
• Consequence: AICDA NM_020661.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.227

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 -10 ACMG points.

• BP6: Variant 12-8604926-CA-C is Benign according to our data. Variant chr12-8604926-CA-C is described in ClinVar as [Likely_benign]. Clinvar id is 1091711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00294 (402/136798) while in subpopulation AFR AF= 0.0107 (392/36570). AF 95% confidence interval is 0.00984. There are 2 homozygotes in gnomad4. There are 188 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AICDA	NM_020661.4	c.428-5delT		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000229335.11	NP_065712.1
AICDA	NM_001330343.2	c.428-35delT		intron_variant	Intron 3 of 4		NP_001317272.1
AICDA	NM_001410970.1	c.427+288delT		intron_variant	Intron 3 of 3		NP_001397899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AICDA	ENST00000229335.11	c.428-5delT		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_020661.4	ENSP00000229335.6

Frequencies

GnomAD3 genomes AF: 0.00295 AC: 403 AN: 136802 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000294

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000608

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00108

GnomAD4 exome AF: 0.00127 AC: 1571 AN: 1235800 Hom.: 1 Cov.: 34 AF XY: 0.00121 AC XY: 747 AN XY: 615628

Gnomad4 AFR exome AF: 0.0207

Gnomad4 AMR exome AF: 0.00632

Gnomad4 ASJ exome AF: 0.00160

Gnomad4 EAS exome AF: 0.00105

Gnomad4 SAS exome AF: 0.00215

Gnomad4 FIN exome AF: 0.00153

Gnomad4 NFE exome AF: 0.000442

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00294 AC: 402 AN: 136798 Hom.: 2 Cov.: 0 AF XY: 0.00287 AC XY: 188 AN XY: 65504

Gnomad4 AFR AF: 0.0107

Gnomad4 AMR AF: 0.000293

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000608

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00108

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hyper-IgM syndrome type 2 Benign:1

Nov 14, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs5796316; hg19: chr12-8757522;