rs11598232

Variant names:

• chr10-74336568-A-T
• rs11598232
• NM_006721.4:c.273+21823A>T

Variant summary

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

The NM_006721.4(ADK):​c.273+21823A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 151,948 control chromosomes in the GnomAD database, including 20,185 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 0.48 (20185 hom., cov: 31)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.966
• Publications: 1 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006721.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	NM_006721.4	MANE Select	c.273+21823A>T		intron	N/A	NP_006712.2
	ADK	NM_001123.4		c.222+21823A>T		intron	N/A	NP_001114.2
	ADK	NM_001202449.2		c.168+21823A>T		intron	N/A	NP_001189378.1	P55263-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	ENST00000539909.6	TSL:2 MANE Select	c.273+21823A>T		intron	N/A	ENSP00000443965.2	P55263-1
	ADK	ENST00000286621.7	TSL:1	c.273+21823A>T		intron	N/A	ENSP00000286621.3	A0A5K1VW54
	ADK	ENST00000372734.5	TSL:1	c.222+21823A>T		intron	N/A	ENSP00000361819.3	P55263-2

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73483 AN: 151828 Hom.: 20193 Cov.: 31

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.483 AC: 73464 AN: 151948 Hom.: 20185 Cov.: 31 AF XY: 0.483 AC XY: 35829 AN XY: 74224

African (AFR) AF: 0.226 AC: 9360 AN: 41472

American (AMR) AF: 0.513 AC: 7835 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2499 AN: 3464

East Asian (EAS) AF: 0.291 AC: 1504 AN: 5168

South Asian (SAS) AF: 0.429 AC: 2062 AN: 4812

European-Finnish (FIN) AF: 0.575 AC: 6043 AN: 10516

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42377 AN: 67928

Other (OTH) AF: 0.546 AC: 1154 AN: 2112

Alfa AF: 0.547 Hom.: 3023

Bravo AF: 0.463

Asia WGS AF: 0.307 AC: 1072 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.1
DANN	Benign	0.39
PhyloP100		0.97
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: rs11598232; hg19: chr10-76096326;