chr10-74536031-A-G

Variant names:

• chr10-74536031-A-G
• rs7924176
• NM_006721.4:c.726+10605A>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.726+10605A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,808 control chromosomes in the GnomAD database, including 9,181 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 0.31 (9181 hom., cov: 30)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 18 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 (NFE) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADK	NM_006721.4	c.726+10605A>G		intron_variant	Intron 7 of 10	ENST00000539909.6	NP_006712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADK	ENST00000539909.6	c.726+10605A>G		intron_variant	Intron 7 of 10	2	NM_006721.4	ENSP00000443965.2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46619 AN: 151690 Hom.: 9183 Cov.: 30

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.307 AC: 46610 AN: 151808 Hom.: 9181 Cov.: 30 AF XY: 0.300 AC XY: 22270 AN XY: 74156

African (AFR) AF: 0.0960 AC: 3976 AN: 41422

American (AMR) AF: 0.305 AC: 4653 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1911 AN: 3470

East Asian (EAS) AF: 0.0205 AC: 106 AN: 5178

South Asian (SAS) AF: 0.214 AC: 1024 AN: 4796

European-Finnish (FIN) AF: 0.339 AC: 3551 AN: 10460

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.444 AC: 30174 AN: 67936

Other (OTH) AF: 0.362 AC: 764 AN: 2110

Alfa AF: 0.404 Hom.: 54955

Bravo AF: 0.295

Asia WGS AF: 0.110 AC: 382 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.4
DANN	Benign	0.76
PhyloP100		1.5
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: rs7924176; hg19: chr10-76295789;