rs10509348

chr10-74382759-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006721.4(ADK):c.274-11382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,808 control chromosomes in the GnomAD database, including 32,450 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 0.64 (32450 hom., cov: 30)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.480

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADK	NM_006721.4	c.274-11382G>A		intron_variant		ENST00000539909.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADK	ENST00000539909.6	c.274-11382G>A		intron_variant		2	NM_006721.4	P3

Frequencies

GnomAD3 genomes AF: 0.639 AC: 96999 AN: 151692 Hom.: 32456 Cov.: 30

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.639 AC: 97032 AN: 151808 Hom.: 32450 Cov.: 30 AF XY: 0.634 AC XY: 47018 AN XY: 74168

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.841

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.701

Alfa AF: 0.684 Hom.: 6140

Bravo AF: 0.630

Asia WGS AF: 0.461 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.35
Dann	Benign	0.37

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: rs10509348; hg19: chr10-76142517;