chr4-122412022-T-C

Variant names:

• chr4-122412022-T-C
• rs12499753
• NM_139243.4:c.1020-558T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139243.4(ADAD1):​c.1020-558T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,962 control chromosomes in the GnomAD database, including 7,564 homozygotes. 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 0.29 (7564 hom., cov: 32)
• Consequence: ADAD1 NM_139243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

Genes affected

ADAD1 (HGNC:30713): (adenosine deaminase domain containing 1) Predicted to enable double-stranded RNA adenosine deaminase activity; double-stranded RNA binding activity; and tRNA-specific adenosine deaminase activity. Predicted to be involved in RNA processing and adenosine to inosine editing. Predicted to act upstream of or within spermatid development. Predicted to be located in nucleus. Predicted to be active in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAD1	NM_139243.4	c.1020-558T>C		intron_variant	Intron 9 of 12	ENST00000296513.7	NP_640336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAD1	ENST00000296513.7	c.1020-558T>C		intron_variant	Intron 9 of 12	2	NM_139243.4	ENSP00000296513.2
ADAD1	ENST00000388724.6	c.987-558T>C		intron_variant	Intron 8 of 11	1		ENSP00000373376.2
ADAD1	ENST00000388725.2	c.966-558T>C		intron_variant	Intron 8 of 11	2		ENSP00000373377.2

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44154 AN: 151844 Hom.: 7563 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.273

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.291 AC: 44155 AN: 151962 Hom.: 7564 Cov.: 32 AF XY: 0.297 AC XY: 22090 AN XY: 74266

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.273

Alfa AF: 0.322 Hom.: 9825

Bravo AF: 0.280

Asia WGS AF: 0.300 AC: 1039 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.9
DANN	Benign	0.86

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

Other links and lift over

dbSNP: rs12499753; hg19: chr4-123333177;