rs11000911

Variant names:

• chr10-74186806-T-C
• rs11000911
• NM_006721.4:c.66-13958T>C

Variant summary

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

The NM_006721.4(ADK):​c.66-13958T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,036 control chromosomes in the GnomAD database, including 22,728 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 0.53 (22728 hom., cov: 32)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.584
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADK	NM_006721.4	c.66-13958T>C		intron_variant	Intron 1 of 10	ENST00000539909.6	NP_006712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADK	ENST00000539909.6	c.66-13958T>C		intron_variant	Intron 1 of 10	2	NM_006721.4	ENSP00000443965.2

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81176 AN: 151918 Hom.: 22725 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.742

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.534 AC: 81188 AN: 152036 Hom.: 22728 Cov.: 32 AF XY: 0.531 AC XY: 39435 AN XY: 74298

African (AFR) AF: 0.403 AC: 16724 AN: 41462

American (AMR) AF: 0.538 AC: 8225 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.742 AC: 2573 AN: 3468

East Asian (EAS) AF: 0.297 AC: 1539 AN: 5184

South Asian (SAS) AF: 0.428 AC: 2059 AN: 4816

European-Finnish (FIN) AF: 0.566 AC: 5958 AN: 10518

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42253 AN: 68002

Other (OTH) AF: 0.582 AC: 1225 AN: 2106

Alfa AF: 0.590 Hom.: 57119

Bravo AF: 0.523

Asia WGS AF: 0.325 AC: 1133 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	6.4
DANN	Benign	0.82
PhyloP100		0.58
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: rs11000911; hg19: chr10-75946564;