rs5796316

chr12-8604926-CAAAAAAAA-Cchr12-8604926-CAAAAAAAA-CAchr12-8604926-CAAAAAAAA-CAAchr12-8604926-CAAAAAAAA-CAAAAAchr12-8604926-CAAAAAAAA-CAAAAAAchr12-8604926-CAAAAAAAA-CAAAAAAAchr12-8604926-CAAAAAAAA-CAAAAAAAAAchr12-8604926-CAAAAAAAA-CAAAAAAAAAAchr12-8604926-CAAAAAAAA-CAAAAAAAAAAAchr12-8604926-CAAAAAAAA-CAAAAAAAAAAAA

Variant summary

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

The NM_020661.4(AICDA):c.428-12_428-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000433 in 1,386,516 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: 𝑓 0.0000073 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: AICDA NM_020661.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61

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/exons	MANE	UniProt
AICDA	NM_020661.4	c.428-12_428-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000229335.11
AICDA	NM_001330343.2	c.428-42_428-35del		intron_variant
AICDA	NM_001410970.1	c.427+281_427+288del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AICDA	ENST00000229335.11	c.428-12_428-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_020661.4	P1

Frequencies

GnomAD3 genomes AF: 0.00000731 AC: 1 AN: 136836 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000155

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000400 AC: 5 AN: 1249680 Hom.: 0 AF XY: 0.00000482 AC XY: 3 AN XY: 622912

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000521

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000731 AC: 1 AN: 136836 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 65504

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000155

Gnomad4 OTH AF: 0.00

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;