dbSNP rs144492760: ADK:c.195-18A>G (chr10-74314649-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

adenosine kinase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

ADK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006721.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADK	NM_006721.4	MANE Select	c.195-18A>G	intron	N/A	NP_006712.2
ADK	NM_001123.4		c.144-18A>G	intron	N/A	NP_001114.2
ADK	NM_001202449.2		c.90-18A>G	intron	N/A	NP_001189378.1	P55263-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADK	ENST00000539909.6	TSL:2 MANE Select	c.195-18A>G	intron	N/A	ENSP00000443965.2	P55263-1
ADK	ENST00000286621.7	TSL:1	c.195-18A>G	intron	N/A	ENSP00000286621.3	A0A5K1VW54
ADK	ENST00000372734.5	TSL:1	c.144-18A>G	intron	N/A	ENSP00000361819.3	P55263-2

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

GnomAD2 exomes

AF:

0.00770

AC:

1908

AN:

247776

AF XY:

0.00777

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 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

African (AFR)

AF:

0.00203

AC:

AN:

32928

American (AMR)

AF:

0.00182

AC:

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.00220

AC:

AN:

25886

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39400

South Asian (SAS)

AF:

0.00569

AC:

486

AN:

85472

European-Finnish (FIN)

AF:

0.00320

AC:

170

AN:

53084

Middle Eastern (MID)

AF:

0.00237

AC:

AN:

5488

European-Non Finnish (NFE)

AF:

0.0145

AC:

15801

AN:

1089842

Other (OTH)

AF:

0.00905

AC:

538

AN:

59432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

791

1583

2374

3166

3957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

582

1164

1746

2328

2910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00817

AC:

1243

AN:

152186

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

569

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.00171

AC:

AN:

41560

American (AMR)

AF:

0.00425

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00455

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0154

AC:

1047

AN:

67920

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

124

187

249

311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00937

Hom.:

Bravo

AF:

0.00740

Asia WGS

AF:

0.00347

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Adenosine kinase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.9

(source)

DANN

Benign

0.86

PhyloP100

-0.91

PromoterAI

0.015

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over