rs7138990

Variant names:

• chr12-8603146-T-A
• rs7138990
• NM_020661.4:c.*1138A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-8603146-T-A
• chr12-8603146-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020661.4(AICDA):​c.*1138A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000766 in 130,482 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000077 (0 hom., cov: 28)
• Consequence: AICDA NM_020661.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• Publications: 0 publications found

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]

AICDA Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 2

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AICDA	NM_020661.4	c.*1138A>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000229335.11	NP_065712.1
AICDA	NM_001330343.2	c.*1138A>T		3_prime_UTR_variant	Exon 5 of 5		NP_001317272.1
AICDA	NM_001410970.1	c.*1181A>T		3_prime_UTR_variant	Exon 4 of 4		NP_001397899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AICDA	ENST00000229335.11	c.*1138A>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_020661.4	ENSP00000229335.6

Frequencies

GnomAD3 genomes AF: 0.00000766 AC: 1 AN: 130482 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000766 AC: 1 AN: 130482 Hom.: 0 Cov.: 28 AF XY: 0.0000157 AC XY: 1 AN XY: 63792

African (AFR) AF: 0.00 AC: 0 AN: 27304

American (AMR) AF: 0.00 AC: 0 AN: 13826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3194

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64214

Other (OTH) AF: 0.00 AC: 0 AN: 1800

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		0.63

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

Other links and lift over

dbSNP: rs7138990; hg19: chr12-8755742;