rs2815324

Positions:

• chr1-77326004-T-C

Variant summary

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

The NM_174858.3(AK5):​c.700-14373T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,162 control chromosomes in the GnomAD database, including 2,234 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 (2234 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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=-0.83).
• 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.700-14373T>C		intron_variant		ENST00000354567.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK5	ENST00000354567.7	c.700-14373T>C		intron_variant		1	NM_174858.3	P1
AK5	ENST00000344720.9	c.622-14373T>C		intron_variant		1
AK5	ENST00000524494.1	n.94-14373T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23191 AN: 152044 Hom.: 2237 Cov.: 32

Gnomad AFR AF: 0.0505

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.152 AC: 23177 AN: 152162 Hom.: 2234 Cov.: 32 AF XY: 0.154 AC XY: 11489 AN XY: 74384

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0951

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.150

Alfa AF: 0.173 Hom.: 325

Bravo AF: 0.136

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.74

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: rs2815324; hg19: chr1-77791689;