rs6838440

Positions:

• chr4-112406922-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.277-4905C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,050 control chromosomes in the GnomAD database, including 10,604 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 0.37 (10604 hom., cov: 32)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK1	NM_025144.4	c.277-4905C>T		intron_variant		ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2	c.277-4905C>T		intron_variant			NP_001095876.1
ALPK1	NM_001253884.2	c.43-4905C>T		intron_variant			NP_001240813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1	c.277-4905C>T		intron_variant			NM_025144.4	ENSP00000498374	P1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55582 AN: 151932 Hom.: 10584 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.332

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.366 AC: 55638 AN: 152050 Hom.: 10604 Cov.: 32 AF XY: 0.366 AC XY: 27160 AN XY: 74298

Gnomad4 AFR AF: 0.482

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.332

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.361

Alfa AF: 0.323 Hom.: 10653

Bravo AF: 0.376

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	9.2
DANN	Benign	0.70

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: rs6838440; hg19: chr4-113328078;