rs571962706

Variant names:

• chr10-74176475-G-A
• rs571962706
• NM_006721.4:c.66-24289G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-74176475-G-A
• chr10-74176475-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006721.4(ADK):​c.66-24289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,139,796 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (5 hom.)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.90
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-74176475-G-A is Benign according to our data. Variant chr10-74176475-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 879389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000125 (19/152318) while in subpopulation SAS AF = 0.00373 (18/4826). AF 95% confidence interval is 0.00241. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	NM_006721.4	MANE Select	c.66-24289G>A		intron	N/A	NP_006712.2
	ADK	NM_001202450.2		c.66-24289G>A		intron	N/A	NP_001189379.1	P55263-3
	ADK	NM_001369123.1		c.66-24289G>A		intron	N/A	NP_001356052.1	A0A5F9ZH31

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	ENST00000539909.6	TSL:2 MANE Select	c.66-24289G>A		intron	N/A	ENSP00000443965.2	P55263-1
	ADK	ENST00000286621.7	TSL:1	c.66-24289G>A		intron	N/A	ENSP00000286621.3	A0A5K1VW54
	ADK	ENST00000960305.1		c.66-24289G>A		intron	N/A	ENSP00000630364.1

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 19 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000158 AC: 156 AN: 987478 Hom.: 5 Cov.: 27 AF XY: 0.000249 AC XY: 116 AN XY: 466690

African (AFR) AF: 0.0000536 AC: 1 AN: 18640

American (AMR) AF: 0.00 AC: 0 AN: 7824

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9258

East Asian (EAS) AF: 0.00 AC: 0 AN: 12368

South Asian (SAS) AF: 0.00387 AC: 151 AN: 39032

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2276

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 853026

Other (OTH) AF: 0.000111 AC: 4 AN: 36094

GnomAD4 genome AF: 0.000125 AC: 19 AN: 152318 Hom.: 0 Cov.: 32 AF XY: 0.000188 AC XY: 14 AN XY: 74474

African (AFR) AF: 0.00 AC: 0 AN: 41582

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Adenosine kinase deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.097
DANN	Benign	0.91
PhyloP100		-2.9
PromoterAI		-0.059	Neutral

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

Other links and lift over

dbSNP: rs571962706; hg19: chr10-75936233;