10-74224248-C-G

Variant names:

• chr10-74224248-C-G
• rs10824119
• NM_006721.4:c.141-290C>G

Variant summary

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

The NM_006721.4(ADK):​c.141-290C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 152,142 control chromosomes in the GnomAD database, including 41,833 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 0.74 (41833 hom., cov: 33)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62
• Publications: 4 publications found

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]

ADK Gene-Disease associations (from GenCC):

• adenosine kinase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADK	NM_006721.4	c.141-290C>G		intron_variant	Intron 2 of 10	ENST00000539909.6	NP_006712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADK	ENST00000539909.6	c.141-290C>G		intron_variant	Intron 2 of 10	2	NM_006721.4	ENSP00000443965.2

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111810 AN: 152024 Hom.: 41800 Cov.: 33

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.735 AC: 111897 AN: 152142 Hom.: 41833 Cov.: 33 AF XY: 0.727 AC XY: 54058 AN XY: 74378

African (AFR) AF: 0.788 AC: 32728 AN: 41522

American (AMR) AF: 0.706 AC: 10783 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3020 AN: 3472

East Asian (EAS) AF: 0.408 AC: 2115 AN: 5182

South Asian (SAS) AF: 0.539 AC: 2599 AN: 4822

European-Finnish (FIN) AF: 0.663 AC: 7006 AN: 10574

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51136 AN: 67974

Other (OTH) AF: 0.774 AC: 1634 AN: 2110

Alfa AF: 0.666 Hom.: 1919

Bravo AF: 0.738

Asia WGS AF: 0.490 AC: 1709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.39
PhyloP100		-1.6
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: rs10824119; hg19: chr10-75984006;