rs11001109

Variant names:

• chr10-74683339-A-G
• rs11001109
• NM_006721.4:c.964+13070A>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.964+13070A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,022 control chromosomes in the GnomAD database, including 35,360 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 0.68 (35360 hom., cov: 32)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADK	NM_006721.4	c.964+13070A>G		intron_variant	Intron 10 of 10	ENST00000539909.6	NP_006712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADK	ENST00000539909.6	c.964+13070A>G		intron_variant	Intron 10 of 10	2	NM_006721.4	ENSP00000443965.2

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103122 AN: 151904 Hom.: 35345 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.679 AC: 103183 AN: 152022 Hom.: 35360 Cov.: 32 AF XY: 0.678 AC XY: 50378 AN XY: 74306

African (AFR) AF: 0.597 AC: 24753 AN: 41448

American (AMR) AF: 0.688 AC: 10507 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2747 AN: 3472

East Asian (EAS) AF: 0.709 AC: 3662 AN: 5166

South Asian (SAS) AF: 0.699 AC: 3368 AN: 4818

European-Finnish (FIN) AF: 0.662 AC: 6990 AN: 10562

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.716 AC: 48686 AN: 67962

Other (OTH) AF: 0.706 AC: 1494 AN: 2116

Alfa AF: 0.681 Hom.: 4629

Bravo AF: 0.680

Asia WGS AF: 0.683 AC: 2373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.64
PhyloP100		-0.25
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: rs11001109; hg19: chr10-76443097;