rs11732095

Variant names:

• chr4-122427190-A-G
• rs11732095
• NM_139243.4:c.1618-2436A>G

Variant summary

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

The NM_139243.4(ADAD1):​c.1618-2436A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 152,334 control chromosomes in the GnomAD database, including 401 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 0.065 (401 hom., cov: 33)
• Consequence: ADAD1 NM_139243.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 8 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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAD1	NM_139243.4	c.1618-2436A>G		intron_variant	Intron 12 of 12	ENST00000296513.7	NP_640336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAD1	ENST00000296513.7	c.1618-2436A>G		intron_variant	Intron 12 of 12	2	NM_139243.4	ENSP00000296513.2
ADAD1	ENST00000388724.6	c.1585-2436A>G		intron_variant	Intron 11 of 11	1		ENSP00000373376.2
ADAD1	ENST00000388725.2	c.1564-2436A>G		intron_variant	Intron 11 of 11	2		ENSP00000373377.2

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9852 AN: 152216 Hom.: 401 Cov.: 33

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0833

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0132

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.0955

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

GnomAD4 genome AF: 0.0647 AC: 9849 AN: 152334 Hom.: 401 Cov.: 33 AF XY: 0.0599 AC XY: 4461 AN XY: 74488

African (AFR) AF: 0.0378 AC: 1572 AN: 41588

American (AMR) AF: 0.0832 AC: 1273 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0130 AC: 63 AN: 4830

European-Finnish (FIN) AF: 0.0221 AC: 235 AN: 10622

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0856 AC: 5819 AN: 68016

Other (OTH) AF: 0.0940 AC: 199 AN: 2116

Alfa AF: 0.0872 Hom.: 1078

Bravo AF: 0.0714

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.90
DANN	Benign	0.48
PhyloP100		-1.1
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: rs11732095; hg19: chr4-123348345;