rs10488907

chr4-112390949-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025144.4(ALPK1):c.276+8397C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,030 control chromosomes in the GnomAD database, including 3,266 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 0.18 (3266 hom., cov: 32)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALPK1	NM_025144.4	c.276+8397C>T		intron_variant		ENST00000650871.1
ALPK1	NM_001102406.2	c.276+8397C>T		intron_variant
ALPK1	NM_001253884.2	c.42+13051C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALPK1	ENST00000650871.1	c.276+8397C>T		intron_variant			NM_025144.4	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27401 AN: 151912 Hom.: 3265 Cov.: 32

Gnomad AFR AF: 0.0481

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.180 AC: 27395 AN: 152030 Hom.: 3266 Cov.: 32 AF XY: 0.180 AC XY: 13341 AN XY: 74304

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.0236

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.200

Alfa AF: 0.221 Hom.: 2336

Bravo AF: 0.167

Asia WGS AF: 0.0630 AC: 221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.14
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs10488907; hg19: chr4-113312105;