4-112386555-C-G

Variant names:

• chr4-112386555-C-G
• rs2051778
• NM_025144.4:c.276+4003C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025144.4(ALPK1):​c.276+4003C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,220 control chromosomes in the GnomAD database, including 60,790 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 0.89 (60790 hom., cov: 31)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 6 publications found

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]

ALPK1 Gene-Disease associations (from GenCC):

• retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025144.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	NM_025144.4	MANE Select	c.276+4003C>G		intron	N/A	NP_079420.3
	ALPK1	NM_001102406.2		c.276+4003C>G		intron	N/A	NP_001095876.1
	ALPK1	NM_001253884.2		c.42+8657C>G		intron	N/A	NP_001240813.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	ENST00000650871.1	MANE Select	c.276+4003C>G		intron	N/A	ENSP00000498374.1
	ALPK1	ENST00000177648.13	TSL:1	c.276+4003C>G		intron	N/A	ENSP00000177648.9
	ALPK1	ENST00000458497.6	TSL:5	c.276+4003C>G		intron	N/A	ENSP00000398048.1

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135631 AN: 152102 Hom.: 60728 Cov.: 31

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.914

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

GnomAD4 genome AF: 0.892 AC: 135754 AN: 152220 Hom.: 60790 Cov.: 31 AF XY: 0.893 AC XY: 66432 AN XY: 74426

African (AFR) AF: 0.974 AC: 40466 AN: 41542

American (AMR) AF: 0.903 AC: 13809 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3232 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4570 AN: 5176

South Asian (SAS) AF: 0.743 AC: 3577 AN: 4816

European-Finnish (FIN) AF: 0.873 AC: 9247 AN: 10596

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57869 AN: 68004

Other (OTH) AF: 0.915 AC: 1934 AN: 2114

Alfa AF: 0.830 Hom.: 2519

Bravo AF: 0.903

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Benign	0.70
PhyloP100		2.5
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: rs2051778; hg19: chr4-113307711;