chr1-77402139-C-G

Variant names:

• chr1-77402139-C-G
• rs17098286
• NM_174858.3:c.892-8842C>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.892-8842C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,144 control chromosomes in the GnomAD database, including 893 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 0.099 (893 hom., cov: 32)
• Consequence: AK5 NM_174858.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 4 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]

ENSG00000233099 (HGNC:40069):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK5	NM_174858.3	c.892-8842C>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.892-8842C>G		intron_variant	Intron 6 of 13	1	NM_174858.3	ENSP00000346577.2

Frequencies

GnomAD3 genomes AF: 0.0983 AC: 14943 AN: 152026 Hom.: 879 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0928

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0736

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.0986 AC: 15000 AN: 152144 Hom.: 893 Cov.: 32 AF XY: 0.0981 AC XY: 7299 AN XY: 74394

African (AFR) AF: 0.136 AC: 5624 AN: 41498

American (AMR) AF: 0.0929 AC: 1421 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 300 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1032 AN: 5164

South Asian (SAS) AF: 0.108 AC: 519 AN: 4820

European-Finnish (FIN) AF: 0.0778 AC: 824 AN: 10592

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0737 AC: 5009 AN: 67992

Other (OTH) AF: 0.106 AC: 224 AN: 2110

Alfa AF: 0.0335 Hom.: 30

Bravo AF: 0.103

Asia WGS AF: 0.200 AC: 694 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.78
PhyloP100		-0.084
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: rs17098286; hg19: chr1-77867824;