NM_020661.4:c.428-8_428-5dupTTTT

Variant names:

• chr12-8604926-C-CAAAA
• rs5796316
• NM_020661.4:c.428-8_428-5dupTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020661.4(AICDA):​c.428-8_428-5dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000064 in 1,249,572 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000064 (0 hom.)
• Consequence: AICDA NM_020661.4 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AICDA	NM_020661.4	c.428-8_428-5dupTTTT		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000229335.11	NP_065712.1
AICDA	NM_001330343.2	c.428-38_428-35dupTTTT		intron_variant	Intron 3 of 4		NP_001317272.1
AICDA	NM_001410970.1	c.427+285_427+288dupTTTT		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.428-8_428-5dupTTTT		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_020661.4	ENSP00000229335.6

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000640 AC: 8 AN: 1249572 Hom.: 0 Cov.: 34 AF XY: 0.0000112 AC XY: 7 AN XY: 622864

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000303

Gnomad4 ASJ exome AF: 0.0000449

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000407

Gnomad4 FIN exome AF: 0.0000232

Gnomad4 NFE exome AF: 0.00000104

Gnomad4 OTH exome AF: 0.0000193

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;