10-74176853-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000372734.5(ADK):c.-20C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 1,607,474 control chromosomes in the GnomAD database, including 421,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41960 hom., cov: 33)
  • Exomes 𝑓: 0.72 (379830 hom.)
• Consequence: ADK ENST00000372734.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.751

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-74176853-C-T is Benign according to our data. Variant chr10-74176853-C-T is described in ClinVar as [Benign]. Clinvar id is 300835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-74176853-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADK	NM_006721.4	c.66-23911C>T		intron_variant		ENST00000539909.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADK	ENST00000539909.6	c.66-23911C>T		intron_variant		2	NM_006721.4	P3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 111934 AN: 152040 Hom.: 41926 Cov.: 33

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.782

GnomAD3 exomes AF: 0.674 AC: 160279 AN: 237720 Hom.: 56112 AF XY: 0.676 AC XY: 87879 AN XY: 130092

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.588

Gnomad ASJ exome AF: 0.872

Gnomad EAS exome AF: 0.370

Gnomad SAS exome AF: 0.553

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.750

Gnomad OTH exome AF: 0.724

GnomAD4 exome AF: 0.717 AC: 1044036 AN: 1455316 Hom.: 379830 Cov.: 77 AF XY: 0.714 AC XY: 517427 AN XY: 724340

Gnomad4 AFR exome AF: 0.790

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.871

Gnomad4 EAS exome AF: 0.392

Gnomad4 SAS exome AF: 0.557

Gnomad4 FIN exome AF: 0.674

Gnomad4 NFE exome AF: 0.741

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.736 AC: 112022 AN: 152158 Hom.: 41960 Cov.: 33 AF XY: 0.727 AC XY: 54102 AN XY: 74374

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.662

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.775

Alfa AF: 0.765 Hom.: 7880

Bravo AF: 0.738

Asia WGS AF: 0.486 AC: 1696 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 08, 2021

- -

Adenosine kinase deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.9
Dann	Benign	0.92

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

Publications

LitVar

Other links and lift over

dbSNP: rs10824095; hg19: chr10-75936611; COSMIC: COSV54206867;