rs2815326

chr1-77333260-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_174858.3(AK5):c.700-7117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,078 control chromosomes in the GnomAD database, including 2,262 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 0.15 (2262 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK5	NM_174858.3	c.700-7117C>T		intron_variant		ENST00000354567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK5	ENST00000354567.7	c.700-7117C>T		intron_variant		1	NM_174858.3	P1
AK5	ENST00000344720.9	c.622-7117C>T		intron_variant		1
AK5	ENST00000524494.1	n.94-7117C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23285 AN: 151960 Hom.: 2265 Cov.: 32

Gnomad AFR AF: 0.0508

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.150

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

GnomAD4 genome AF: 0.153 AC: 23271 AN: 152078 Hom.: 2262 Cov.: 32 AF XY: 0.155 AC XY: 11531 AN XY: 74326

Gnomad4 AFR AF: 0.0507

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0949

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.150

Alfa AF: 0.169 Hom.: 375

Bravo AF: 0.137

Asia WGS AF: 0.134 AC: 466 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	4.2
Dann	Benign	0.61

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

Other links and lift over

dbSNP: rs2815326; hg19: chr1-77798945;