4-112408309-C-T

Variant names:

• chr4-112408309-C-T
• rs7688190
• NM_025144.4:c.277-3518C>T

Variant summary

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

The NM_025144.4(ALPK1):​c.277-3518C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 151,930 control chromosomes in the GnomAD database, including 9,490 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 0.35 (9490 hom., cov: 31)
• Consequence: ALPK1 NM_025144.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALPK1	NM_025144.4	c.277-3518C>T		intron_variant	Intron 4 of 15	ENST00000650871.1	NP_079420.3
ALPK1	NM_001102406.2	c.277-3518C>T		intron_variant	Intron 4 of 15		NP_001095876.1
ALPK1	NM_001253884.2	c.43-3518C>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.277-3518C>T		intron_variant	Intron 4 of 15		NM_025144.4	ENSP00000498374.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 52951 AN: 151814 Hom.: 9469 Cov.: 31

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.349 AC: 53004 AN: 151930 Hom.: 9490 Cov.: 31 AF XY: 0.347 AC XY: 25793 AN XY: 74244

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.357

Alfa AF: 0.316 Hom.: 10778

Bravo AF: 0.355

Asia WGS AF: 0.390 AC: 1360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.010
DANN	Benign	0.34

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: rs7688190; hg19: chr4-113329465;