chr10-74423983-C-T

Variant names:

• chr10-74423983-C-T
• rs1871084
• NM_006721.4:c.555+25404C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006721.4(ADK):​c.555+25404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 161,240 control chromosomes in the GnomAD database, including 42,938 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (40454 hom., cov: 31)
  • Exomes 𝑓: 0.72 (2484 hom.)
• Consequence: ADK NM_006721.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 3 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]

RAB5CP1 (HGNC:45104): (RAB5C, member RAS oncogene family pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

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.555+25404C>T		intron	N/A	NP_006712.2
	ADK	NM_001123.4		c.504+25404C>T		intron	N/A	NP_001114.2
	ADK	NM_001202449.2		c.450+25404C>T		intron	N/A	NP_001189378.1	P55263-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADK	ENST00000539909.6	TSL:2 MANE Select	c.555+25404C>T		intron	N/A	ENSP00000443965.2	P55263-1
	ADK	ENST00000286621.7	TSL:1	c.555+25404C>T		intron	N/A	ENSP00000286621.3	A0A5K1VW54
	ADK	ENST00000372734.5	TSL:1	c.504+25404C>T		intron	N/A	ENSP00000361819.3	P55263-2

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109924 AN: 151808 Hom.: 40425 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.775

GnomAD4 exome AF: 0.720 AC: 6712 AN: 9316 Hom.: 2484 Cov.: 0 AF XY: 0.716 AC XY: 3649 AN XY: 5094

African (AFR) AF: 0.793 AC: 119 AN: 150

American (AMR) AF: 0.661 AC: 152 AN: 230

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 191 AN: 212

East Asian (EAS) AF: 0.415 AC: 88 AN: 212

South Asian (SAS) AF: 0.596 AC: 929 AN: 1558

European-Finnish (FIN) AF: 0.692 AC: 480 AN: 694

Middle Eastern (MID) AF: 0.882 AC: 194 AN: 220

European-Non Finnish (NFE) AF: 0.757 AC: 4159 AN: 5494

Other (OTH) AF: 0.733 AC: 400 AN: 546

GnomAD4 genome AF: 0.724 AC: 110003 AN: 151924 Hom.: 40454 Cov.: 31 AF XY: 0.716 AC XY: 53187 AN XY: 74234

African (AFR) AF: 0.748 AC: 30989 AN: 41438

American (AMR) AF: 0.700 AC: 10707 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.868 AC: 3011 AN: 3470

East Asian (EAS) AF: 0.414 AC: 2123 AN: 5128

South Asian (SAS) AF: 0.539 AC: 2590 AN: 4808

European-Finnish (FIN) AF: 0.663 AC: 7000 AN: 10558

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51090 AN: 67920

Other (OTH) AF: 0.769 AC: 1620 AN: 2108

Alfa AF: 0.744 Hom.: 6363

Bravo AF: 0.725

Asia WGS AF: 0.492 AC: 1713 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.0
DANN	Benign	0.68
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs1871084; hg19: chr10-76183741;