4-112287558-A-G

Variant names:

• chr4-112287558-A-G
• rs7668738
• ENST00000514594.1:n.253+1797A>G

Variant summary

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

The ENST00000514594.1(ALPK1):​n.253+1797A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 152,298 control chromosomes in the GnomAD database, including 170 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 0.033 (170 hom., cov: 32)
• Consequence: ALPK1 ENST00000514594.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568
• Publications: 2 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: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000514594.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	ENST00000514594.1	TSL:3	n.253+1797A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0329 AC: 5001 AN: 152180 Hom.: 166 Cov.: 32

Gnomad AFR AF: 0.0742

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.0381

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.00725

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.00466

Gnomad OTH AF: 0.0411

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

GnomAD4 genome AF: 0.0329 AC: 5015 AN: 152298 Hom.: 170 Cov.: 32 AF XY: 0.0335 AC XY: 2497 AN XY: 74482

African (AFR) AF: 0.0745 AC: 3095 AN: 41560

American (AMR) AF: 0.0238 AC: 365 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0381 AC: 132 AN: 3466

East Asian (EAS) AF: 0.153 AC: 792 AN: 5184

South Asian (SAS) AF: 0.00705 AC: 34 AN: 4822

European-Finnish (FIN) AF: 0.0155 AC: 165 AN: 10616

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.00466 AC: 317 AN: 68020

Other (OTH) AF: 0.0402 AC: 85 AN: 2116

Alfa AF: 0.0105 Hom.: 9

Bravo AF: 0.0373

Asia WGS AF: 0.0810 AC: 281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		0.57

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7668738;

hg19: chr4-113208714;