rs4833407

Positions:

• chr4-112390634-C-A
• chr4-112390634-C-G
• chr4-112390634-C-T

Variant summary

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

The NM_025144.4(ALPK1):​c.276+8082C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 151,848 control chromosomes in the GnomAD database, including 20,282 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 0.51 (20282 hom., cov: 31)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK1	NM_025144.4	c.276+8082C>A		intron_variant		ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2	c.276+8082C>A		intron_variant			NP_001095876.1
ALPK1	NM_001253884.2	c.42+12736C>A		intron_variant			NP_001240813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1	c.276+8082C>A		intron_variant			NM_025144.4	ENSP00000498374.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76873 AN: 151730 Hom.: 20245 Cov.: 31

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.470

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.507 AC: 76967 AN: 151848 Hom.: 20282 Cov.: 31 AF XY: 0.512 AC XY: 37957 AN XY: 74198

Gnomad4 AFR AF: 0.628

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.699

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.494

Alfa AF: 0.428 Hom.: 15108

Bravo AF: 0.525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.37

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: rs4833407; hg19: chr4-113311790;