rs6827839

Variant names:

• chr4-122417860-G-A
• rs6827839
• NM_139243.4:c.1487+2244G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADAD1	NM_139243.4	c.1487+2244G>A		intron_variant	Intron 11 of 12	ENST00000296513.7	NP_640336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAD1	ENST00000296513.7	c.1487+2244G>A		intron_variant	Intron 11 of 12	2	NM_139243.4	ENSP00000296513.2
ADAD1	ENST00000388724.6	c.1454+2244G>A		intron_variant	Intron 10 of 11	1		ENSP00000373376.2
ADAD1	ENST00000388725.2	c.1433+2244G>A		intron_variant	Intron 10 of 11	2		ENSP00000373377.2

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

African (AFR) AF: 0.601 AC: 24908 AN: 41414

American (AMR) AF: 0.398 AC: 6079 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1993 AN: 5164

South Asian (SAS) AF: 0.573 AC: 2763 AN: 4826

European-Finnish (FIN) AF: 0.388 AC: 4085 AN: 10534

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.381 AC: 25913 AN: 67956

Other (OTH) AF: 0.468 AC: 987 AN: 2110

Alfa AF: 0.431 Hom.: 3630

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
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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: rs6827839; hg19: chr4-123339015;