rs6827839

Positions:

• chr4-122417860-G-A

Variant summary

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

The NM_139243.4(ADAD1):​c.1487+2244G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,946 control chromosomes in the GnomAD database, including 16,395 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 0.45 (16395 hom., cov: 32)
• Consequence: ADAD1 NM_139243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAD1	NM_139243.4	c.1487+2244G>A		intron_variant		ENST00000296513.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAD1	ENST00000296513.7	c.1487+2244G>A		intron_variant		2	NM_139243.4	P1
ADAD1	ENST00000388724.6	c.1454+2244G>A		intron_variant		1
ADAD1	ENST00000388725.2	c.1433+2244G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68880 AN: 151828 Hom.: 16361 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.388

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.454 AC: 68968 AN: 151946 Hom.: 16395 Cov.: 32 AF XY: 0.457 AC XY: 33935 AN XY: 74278

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.492

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.388

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.468

Alfa AF: 0.420 Hom.: 2959

Bravo AF: 0.456

Asia WGS AF: 0.523 AC: 1819 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.38
DANN	Benign	0.31

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: rs6827839; hg19: chr4-123339015;