rs1109374

Positions:

• chr1-65167814-T-C
• chr1-65167814-T-G

Variant summary

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

The NM_013410.4(AK4):​c.145+19262T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,014 control chromosomes in the GnomAD database, including 6,059 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 0.27 (6059 hom., cov: 32)
• Consequence: AK4 NM_013410.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963

Genes affected

AK4 (HGNC:363): (adenylate kinase 4) This gene encodes a member of the adenylate kinase family of enzymes. The encoded protein is localized to the mitochondrial matrix. Adenylate kinases regulate the adenine and guanine nucleotide compositions within a cell by catalyzing the reversible transfer of phosphate group among these nucleotides. Five isozymes of adenylate kinase have been identified in vertebrates. Expression of these isozymes is tissue-specific and developmentally regulated. A pseudogene for this gene has been located on chromosome 17. Three transcript variants encoding the same protein have been identified for this gene. Sequence alignment suggests that the gene defined by NM_013410, NM_203464, and NM_001005353 is located on chromosome 1. [provided by RefSeq, Jul 2008]

AK4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK4	NM_013410.4	c.145+19262T>C		intron_variant		ENST00000327299.8	NP_037542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK4	ENST00000327299.8	c.145+19262T>C		intron_variant		1	NM_013410.4	ENSP00000322175.7

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41418 AN: 151896 Hom.: 6056 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.575

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.273 AC: 41440 AN: 152014 Hom.: 6059 Cov.: 32 AF XY: 0.273 AC XY: 20319 AN XY: 74318

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.574

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.264

Alfa AF: 0.236 Hom.: 1949

Bravo AF: 0.276

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.11
DANN	Benign	0.56

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: rs1109374; hg19: chr1-65633497;