chr4-112299646-T-C

Position:

• chr4-112299646-T-C

Variant summary

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

The NM_025144.4(ALPK1):​c.-153+2177T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,082 control chromosomes in the GnomAD database, including 30,934 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 0.62 (30934 hom., cov: 32)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ALPK1	NM_025144.4	c.-153+2177T>C		intron_variant		ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2	c.-101+2177T>C		intron_variant			NP_001095876.1
ALPK1	NM_001253884.2	c.-180+2177T>C		intron_variant			NP_001240813.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ALPK1	ENST00000650871.1	c.-153+2177T>C		intron_variant			NM_025144.4	ENSP00000498374.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93570 AN: 151964 Hom.: 30889 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.714

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.616 AC: 93662 AN: 152082 Hom.: 30934 Cov.: 32 AF XY: 0.611 AC XY: 45384 AN XY: 74336

Gnomad4 AFR AF: 0.864

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.614

Alfa AF: 0.522 Hom.: 17025

Bravo AF: 0.647

Asia WGS AF: 0.490 AC: 1706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.86

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: rs6533603; hg19: chr4-113220802;