Variant 12-8602590-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_020661.4(AICDA):c.*1694A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0208 in 152,278 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 125 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

AICDA
NM_020661.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.909

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-8602590-T-C is Benign according to our data. Variant chr12-8602590-T-C is described in ClinVar as [Benign]. Clinvar id is 310548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
AICDA	NM_020661.4 linkuse as main transcript	c.*1694A>G	3_prime_UTR_variant	5/5	ENST00000229335.11	NP_065712.1
AICDA	NM_001330343.2 linkuse as main transcript	c.*1694A>G	3_prime_UTR_variant	5/5		NP_001317272.1
AICDA	NM_001410970.1 linkuse as main transcript	c.*1737A>G	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 linkuse as main transcript	c.*1694A>G		3_prime_UTR_variant	5/5	1	NM_020661.4	ENSP00000229335	P1	Q9GZX7-1

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3173

AN:

152160

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0741

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0124

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

GnomAD4 genome

AF:

0.0208

AC:

3173

AN:

152278

Hom.:

125

Cov.:

AF XY:

0.0198

AC XY:

1473

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0739

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0152

Hom.:

Bravo

AF:

0.0230

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hyper-IgM syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.1

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over