Variant rs144492760 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006721.4(ADK):c.195-18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,588,270 control chromosomes in the GnomAD database, including 138 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 9 hom., cov: 33)

Exomes 𝑓: 0.012 ( 129 hom. )

Consequence

ADK
NM_006721.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.913

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 10-74314649-A-G is Benign according to our data. Variant chr10-74314649-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 445533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00817 (1243/152186) while in subpopulation NFE AF= 0.0154 (1047/67920). AF 95% confidence interval is 0.0146. There are 9 homozygotes in gnomad4. There are 569 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1243 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADK	NM_006721.4 linkuse as main transcript	c.195-18A>G		intron_variant		ENST00000539909.6	NP_006712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADK	ENST00000539909.6 linkuse as main transcript	c.195-18A>G		intron_variant		2	NM_006721.4	ENSP00000443965	P3	P55263-1

Frequencies

GnomAD3 genomes

AF:

0.00817

AC:

1243

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00434

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00770

AC:

1908

AN:

247776

Hom.:

AF XY:

0.00777

AC XY:

1041

AN XY:

133936

show subpopulations

Gnomad AFR exome

AF:

0.00176

Gnomad AMR exome

AF:

0.00169

Gnomad ASJ exome

AF:

0.00191

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00436

Gnomad FIN exome

AF:

0.00238

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.00695

GnomAD4 exome

AF:

0.0120

AC:

17214

AN:

1436084

Hom.:

129

Cov.:

AF XY:

0.0118

AC XY:

8412

AN XY:

715774

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.00220

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.00569

Gnomad4 FIN exome

AF:

0.00320

Gnomad4 NFE exome

AF:

0.0145

Gnomad4 OTH exome

AF:

0.00905

GnomAD4 genome

AF:

0.00817

AC:

1243

AN:

152186

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

569

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00455

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.0154

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00937

Hom.:

Bravo

AF:

0.00740

Asia WGS

AF:

0.00347

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 18, 2017	- -

Adenosine kinase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 20, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.9

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over