NM_139243.4:c.1488-1257G>A

Variant names:

• chr4-122420004-G-A
• rs7684187
• NM_139243.4:c.1488-1257G>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.1488-1257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,090 control chromosomes in the GnomAD database, including 43,739 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 0.76 (43739 hom., cov: 32)
• Consequence: ADAD1 NM_139243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 15 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.842 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAD1	NM_139243.4	c.1488-1257G>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.1488-1257G>A		intron_variant	Intron 11 of 12	2	NM_139243.4	ENSP00000296513.2
ADAD1	ENST00000388724.6	c.1455-1257G>A		intron_variant	Intron 10 of 11	1		ENSP00000373376.2
ADAD1	ENST00000388725.2	c.1434-1257G>A		intron_variant	Intron 10 of 11	2		ENSP00000373377.2

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115021 AN: 151972 Hom.: 43702 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.757 AC: 115111 AN: 152090 Hom.: 43739 Cov.: 32 AF XY: 0.766 AC XY: 56988 AN XY: 74378

African (AFR) AF: 0.760 AC: 31524 AN: 41472

American (AMR) AF: 0.802 AC: 12247 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2440 AN: 3472

East Asian (EAS) AF: 0.863 AC: 4455 AN: 5162

South Asian (SAS) AF: 0.836 AC: 4026 AN: 4814

European-Finnish (FIN) AF: 0.859 AC: 9105 AN: 10596

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48965 AN: 67980

Other (OTH) AF: 0.747 AC: 1580 AN: 2114

Alfa AF: 0.731 Hom.: 173721

Bravo AF: 0.751

Asia WGS AF: 0.822 AC: 2858 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.46
DANN	Benign	0.34
PhyloP100		-0.30
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: rs7684187; hg19: chr4-123341159;