rs6812485

Variant names:

• chr4-112410634-G-T
• rs6812485
• NM_025144.4:c.277-1193G>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.277-1193G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,076 control chromosomes in the GnomAD database, including 5,701 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 0.27 (5701 hom., cov: 32)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821
• Publications: 7 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.292 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.277-1193G>T		intron	N/A	NP_079420.3
	ALPK1	NM_001102406.2		c.277-1193G>T		intron	N/A	NP_001095876.1
	ALPK1	NM_001253884.2		c.43-1193G>T		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.277-1193G>T		intron	N/A	ENSP00000498374.1
	ALPK1	ENST00000177648.13	TSL:1	c.277-1193G>T		intron	N/A	ENSP00000177648.9
	ALPK1	ENST00000458497.6	TSL:5	c.277-1193G>T		intron	N/A	ENSP00000398048.1

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40576 AN: 151958 Hom.: 5697 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0925

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.267 AC: 40595 AN: 152076 Hom.: 5701 Cov.: 32 AF XY: 0.265 AC XY: 19708 AN XY: 74334

African (AFR) AF: 0.252 AC: 10455 AN: 41464

American (AMR) AF: 0.211 AC: 3221 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3468

East Asian (EAS) AF: 0.0927 AC: 480 AN: 5178

South Asian (SAS) AF: 0.167 AC: 803 AN: 4820

European-Finnish (FIN) AF: 0.330 AC: 3482 AN: 10560

Middle Eastern (MID) AF: 0.308 AC: 90 AN: 292

European-Non Finnish (NFE) AF: 0.295 AC: 20053 AN: 67990

Other (OTH) AF: 0.265 AC: 559 AN: 2108

Alfa AF: 0.281 Hom.: 3979

Bravo AF: 0.256

Asia WGS AF: 0.130 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.096
DANN	Benign	0.56
PhyloP100		-0.82
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: rs6812485; hg19: chr4-113331790;