rs12573590

Positions:

• chr10-74161058-C-A
• chr10-74161058-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006721.4(ADK):​c.65+9715C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 152,244 control chromosomes in the GnomAD database, including 41 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 0.018 (41 hom., cov: 32)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450

Genes affected

ADK (HGNC:257): (adenosine kinase) This gene an enzyme which catalyzes the transfer of the gamma-phosphate from ATP to adenosine, thereby serving as a regulator of concentrations of both extracellular adenosine and intracellular adenine nucleotides. Adenosine has widespread effects on the cardiovascular, nervous, respiratory, and immune systems and inhibitors of the enzyme could play an important pharmacological role in increasing intravascular adenosine concentrations and acting as anti-inflammatory agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0178 (2712/152244) while in subpopulation NFE AF= 0.0256 (1744/68010). AF 95% confidence interval is 0.0246. There are 41 homozygotes in gnomad4. There are 1325 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2712 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADK	NM_006721.4	c.65+9715C>A		intron_variant		ENST00000539909.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADK	ENST00000539909.6	c.65+9715C>A		intron_variant		2	NM_006721.4	P3

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2712 AN: 152126 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00812

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.0211

Gnomad SAS AF: 0.0196

Gnomad FIN AF: 0.0299

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0256

Gnomad OTH AF: 0.0183

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

GnomAD4 genome AF: 0.0178 AC: 2712 AN: 152244 Hom.: 41 Cov.: 32 AF XY: 0.0178 AC XY: 1325 AN XY: 74432

Gnomad4 AFR AF: 0.00474

Gnomad4 AMR AF: 0.00810

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.0214

Gnomad4 SAS AF: 0.0197

Gnomad4 FIN AF: 0.0299

Gnomad4 NFE AF: 0.0256

Gnomad4 OTH AF: 0.0176

Alfa AF: 0.0145 Hom.: 3

Bravo AF: 0.0148

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.64

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: rs12573590; hg19: chr10-75920816;