Variant 10-74176853-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.751

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=-0.78).

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	Protein	UniProt
ADK	NM_006721.4 linkuse as main transcript	c.66-23911C>T		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.66-23911C>T		intron_variant		2	NM_006721.4	ENSP00000443965	P3	P55263-1

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111934

AN:

152040

Hom.:

41926

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.714

AC XY:

517427

AN XY:

724340

show subpopulations

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.:

AF XY:

0.727

AC XY:

54102

AN XY:

74374

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

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