rs6812485

Positions:

• chr4-112410634-G-T

Variant summary

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

The NM_025144.4(ALPK1):​c.277-1193G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,076 control chromosomes in the GnomAD database, including 5,701 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 (5701 hom., cov: 32)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821

Genes affected

ALPK1 (HGNC:20917): (alpha kinase 1) This gene encodes an alpha kinase. Mice which were homozygous for disrupted copies of this gene exhibited coordination defects (PMID: 21208416). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALPK1	NM_025144.4	c.277-1193G>T		intron_variant		ENST00000650871.1
ALPK1	NM_001102406.2	c.277-1193G>T		intron_variant
ALPK1	NM_001253884.2	c.43-1193G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALPK1	ENST00000650871.1	c.277-1193G>T		intron_variant			NM_025144.4	P1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40576 AN: 151958 Hom.: 5697 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0925

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.267 AC: 40595 AN: 152076 Hom.: 5701 Cov.: 32 AF XY: 0.265 AC XY: 19708 AN XY: 74334

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.0927

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.265

Alfa AF: 0.278 Hom.: 3594

Bravo AF: 0.256

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.096
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: rs6812485; hg19: chr4-113331790;