rs6814233

Variant names:

• chr4-122392977-G-T
• rs6814233
• NM_139243.4:c.530-612G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139243.4(ADAD1):​c.530-612G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 150,610 control chromosomes in the GnomAD database, including 5,643 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 0.25 (5643 hom., cov: 30)
• Consequence: ADAD1 NM_139243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAD1	NM_139243.4	c.530-612G>T		intron_variant	Intron 5 of 12	ENST00000296513.7	NP_640336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAD1	ENST00000296513.7	c.530-612G>T		intron_variant	Intron 5 of 12	2	NM_139243.4	ENSP00000296513.2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37431 AN: 150530 Hom.: 5628 Cov.: 30

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.249 AC: 37466 AN: 150610 Hom.: 5643 Cov.: 30 AF XY: 0.255 AC XY: 18721 AN XY: 73510

African (AFR) AF: 0.0735 AC: 3018 AN: 41068

American (AMR) AF: 0.300 AC: 4533 AN: 15124

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1491 AN: 3460

East Asian (EAS) AF: 0.339 AC: 1733 AN: 5112

South Asian (SAS) AF: 0.506 AC: 2427 AN: 4800

European-Finnish (FIN) AF: 0.295 AC: 2955 AN: 10026

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20214 AN: 67728

Other (OTH) AF: 0.301 AC: 630 AN: 2092

Alfa AF: 0.264 Hom.: 1132

Bravo AF: 0.237

Asia WGS AF: 0.422 AC: 1464 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-0.035
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: rs6814233; hg19: chr4-123314132;