rs4930557

Variant names:

• chr11-68110690-C-T
• rs4930557
• NM_001277.3:c.350+10138G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001277.3(CHKA):​c.350+10138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 151,880 control chromosomes in the GnomAD database, including 24,746 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 0.57 (24746 hom., cov: 31)
• Consequence: CHKA NM_001277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105
• Publications: 6 publications found

Genes affected

CHKA (HGNC:1937): (choline kinase alpha) The major pathway for the biosynthesis of phosphatidylcholine occurs via the CDP-choline pathway. The protein encoded by this gene is the initial enzyme in the sequence and may play a regulatory role. The encoded protein also catalyzes the phosphorylation of ethanolamine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CHKA Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with microcephaly, movement abnormalities, and seizures

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277.3. 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
	CHKA	NM_001277.3	MANE Select	c.350+10138G>A		intron	N/A	NP_001268.2
	CHKA	NM_001376219.1		c.350+10138G>A		intron	N/A	NP_001363148.1
	CHKA	NM_212469.2		c.350+10138G>A		intron	N/A	NP_997634.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKA	ENST00000265689.9	TSL:1 MANE Select	c.350+10138G>A		intron	N/A	ENSP00000265689.4
	CHKA	ENST00000356135.9	TSL:1	c.350+10138G>A		intron	N/A	ENSP00000348454.4
	CHKA	ENST00000531341.1	TSL:3	c.-17+10100G>A		intron	N/A	ENSP00000435032.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86439 AN: 151762 Hom.: 24735 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.569 AC: 86489 AN: 151880 Hom.: 24746 Cov.: 31 AF XY: 0.574 AC XY: 42625 AN XY: 74216

African (AFR) AF: 0.519 AC: 21494 AN: 41378

American (AMR) AF: 0.659 AC: 10067 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2148 AN: 3470

East Asian (EAS) AF: 0.636 AC: 3288 AN: 5172

South Asian (SAS) AF: 0.686 AC: 3305 AN: 4818

European-Finnish (FIN) AF: 0.586 AC: 6174 AN: 10540

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38095 AN: 67928

Other (OTH) AF: 0.591 AC: 1244 AN: 2106

Alfa AF: 0.572 Hom.: 7746

Bravo AF: 0.577

Asia WGS AF: 0.630 AC: 2192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.9
DANN	Benign	0.93
PhyloP100		0.10
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: rs4930557; hg19: chr11-67878157;