rs2054017

Variant names:

• chr1-77345427-A-G
• rs2054017
• NM_174858.3:c.891+4859A>G

Variant summary

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

The NM_174858.3(AK5):​c.891+4859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 152,284 control chromosomes in the GnomAD database, including 761 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 0.091 (761 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• Publications: 2 publications found

Genes affected

AK5 (HGNC:365): (adenylate kinase 5) This gene encodes a member of the adenylate kinase family, which is involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. This member is related to the UMP/CMP kinase of several species. It is located in the cytosol and expressed exclusively in brain. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK5	NM_174858.3	c.891+4859A>G		intron_variant	Intron 6 of 13	ENST00000354567.7	NP_777283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK5	ENST00000354567.7	c.891+4859A>G		intron_variant	Intron 6 of 13	1	NM_174858.3	ENSP00000346577.2
AK5	ENST00000344720.9	c.813+4859A>G		intron_variant	Intron 6 of 13	1		ENSP00000341430.5
AK5	ENST00000465146.5	n.164+4859A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13827 AN: 152166 Hom.: 751 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0769

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0615

Gnomad OTH AF: 0.0809

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0911 AC: 13871 AN: 152284 Hom.: 761 Cov.: 32 AF XY: 0.0933 AC XY: 6952 AN XY: 74476

African (AFR) AF: 0.125 AC: 5176 AN: 41560

American (AMR) AF: 0.0757 AC: 1158 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0862 AC: 299 AN: 3468

East Asian (EAS) AF: 0.201 AC: 1043 AN: 5178

South Asian (SAS) AF: 0.200 AC: 962 AN: 4822

European-Finnish (FIN) AF: 0.0769 AC: 816 AN: 10616

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0616 AC: 4189 AN: 68036

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0767 Hom.: 321

Bravo AF: 0.0915

Asia WGS AF: 0.231 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.80
DANN	Benign	0.82
PhyloP100		-0.29
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: rs2054017; hg19: chr1-77811112;