rs2287652

Positions:

• chr14-77931105-A-G
• chr14-77931105-A-T

Variant summary

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

The NM_020421.4(ADCK1):​c.1207-413A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 152,144 control chromosomes in the GnomAD database, including 1,808 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 0.14 (1808 hom., cov: 32)
• Consequence: ADCK1 NM_020421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282

Genes affected

ADCK1 (HGNC:19038): (aarF domain containing kinase 1) Predicted to enable ATP binding activity and protein serine/threonine kinase activity. Involved in negative regulation of mitochondrial fusion and positive regulation of cristae formation. Predicted to be located in extracellular region. Predicted to be active in mitochondrial inner membrane. Predicted to be integral component of mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCK1	NM_020421.4	c.1207-413A>G		intron_variant		ENST00000238561.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCK1	ENST00000238561.10	c.1207-413A>G		intron_variant		1	NM_020421.4	P1
ADCK1	ENST00000341211.5	c.1003-413A>G		intron_variant		2
ADCK1	ENST00000555217.1	n.1574-413A>G		intron_variant, non_coding_transcript_variant		2
ADCK1	ENST00000556560.5	n.551-413A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21654 AN: 152026 Hom.: 1809 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0897

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.142 AC: 21654 AN: 152144 Hom.: 1808 Cov.: 32 AF XY: 0.144 AC XY: 10705 AN XY: 74380

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0896

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.137

Alfa AF: 0.116 Hom.: 551

Bravo AF: 0.143

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.6
DANN	Benign	0.83

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: rs2287652; hg19: chr14-78397448;