10-74151518-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006721.4(ADK):c.65+175C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,186 control chromosomes in the GnomAD database, including 1,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (1647 hom., cov: 32)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.68

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 10-74151518-C-A is Benign according to our data. Variant chr10-74151518-C-A is described in ClinVar as [Benign]. Clinvar id is 1250012.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADK	NM_006721.4	c.65+175C>A		intron_variant		ENST00000539909.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADK	ENST00000539909.6	c.65+175C>A		intron_variant		2	NM_006721.4	P3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21866 AN: 152068 Hom.: 1636 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0958

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.144 AC: 21912 AN: 152186 Hom.: 1647 Cov.: 32 AF XY: 0.141 AC XY: 10513 AN XY: 74414

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0981

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.0958

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.156

Alfa AF: 0.129 Hom.: 1246

Bravo AF: 0.150

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.75
Dann	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11000897; hg19: chr10-75911276;