rs4833407

Variant names:

• chr4-112390634-C-A
• rs4833407
• NM_025144.4:c.276+8082C>A

Your query was ambiguous. Multiple possible variants found:

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

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+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
• Publications: 19 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, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	NM_025144.4	MANE Select	c.276+8082C>A		intron	N/A	NP_079420.3
	ALPK1	NM_001102406.2		c.276+8082C>A		intron	N/A	NP_001095876.1	Q96QP1-1
	ALPK1	NM_001253884.2		c.42+12736C>A		intron	N/A	NP_001240813.1	Q96QP1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALPK1	ENST00000650871.1	MANE Select	c.276+8082C>A		intron	N/A	ENSP00000498374.1	Q96QP1-1
	ALPK1	ENST00000177648.13	TSL:1	c.276+8082C>A		intron	N/A	ENSP00000177648.9	Q96QP1-1
	ALPK1	ENST00000909431.1		c.276+8082C>A		intron	N/A	ENSP00000579490.1

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

African (AFR) AF: 0.628 AC: 25987 AN: 41408

American (AMR) AF: 0.581 AC: 8869 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3468

East Asian (EAS) AF: 0.699 AC: 3597 AN: 5146

South Asian (SAS) AF: 0.530 AC: 2543 AN: 4798

European-Finnish (FIN) AF: 0.442 AC: 4650 AN: 10524

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.416 AC: 28257 AN: 67928

Other (OTH) AF: 0.494 AC: 1044 AN: 2114

Alfa AF: 0.451 Hom.: 33965

Bravo AF: 0.525

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.40
DANN	Benign	0.37
PhyloP100		-0.56
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: rs4833407; hg19: chr4-113311790;