chr4-112406922-C-T

Variant names:

• chr4-112406922-C-T
• rs6838440
• NM_025144.4:c.277-4905C>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.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
• Publications: 4 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=-0.98).
• 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 rank	MANE	Protein	UniProt
ALPK1	NM_025144.4	c.277-4905C>T		intron_variant	Intron 4 of 15	ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2	c.277-4905C>T		intron_variant	Intron 4 of 15		NP_001095876.1
ALPK1	NM_001253884.2	c.43-4905C>T		intron_variant	Intron 3 of 14		NP_001240813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1	c.277-4905C>T		intron_variant	Intron 4 of 15		NM_025144.4	ENSP00000498374.1

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

African (AFR) AF: 0.482 AC: 19990 AN: 41482

American (AMR) AF: 0.328 AC: 5003 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1921 AN: 5162

South Asian (SAS) AF: 0.275 AC: 1326 AN: 4822

European-Finnish (FIN) AF: 0.332 AC: 3502 AN: 10550

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21163 AN: 67976

Other (OTH) AF: 0.361 AC: 762 AN: 2110

Alfa AF: 0.328 Hom.: 26826

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
PhyloP100		0.30
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: rs6838440; hg19: chr4-113328078;