rs2511439

Variant names:

• chr11-68086568-T-C
• rs2511439
• NM_001277.3:c.463-5111A>G

Variant summary

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

The NM_001277.3(CHKA):​c.463-5111A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 152,302 control chromosomes in the GnomAD database, including 60,675 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 0.89 (60675 hom., cov: 33)
• Consequence: CHKA NM_001277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHKA	NM_001277.3	c.463-5111A>G		intron_variant	Intron 2 of 11	ENST00000265689.9	NP_001268.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHKA	ENST00000265689.9	c.463-5111A>G		intron_variant	Intron 2 of 11	1	NM_001277.3	ENSP00000265689.4
CHKA	ENST00000356135.9	c.462+10451A>G		intron_variant	Intron 2 of 10	1		ENSP00000348454.4
CHKA	ENST00000531341.1	c.97-5111A>G		intron_variant	Intron 2 of 5	3		ENSP00000435032.1
CHKA	ENST00000528235.5	n.60+3253A>G		intron_variant	Intron 1 of 7	5

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135745 AN: 152184 Hom.: 60623 Cov.: 33

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.967

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.913

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.887

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

GnomAD4 genome AF: 0.892 AC: 135856 AN: 152302 Hom.: 60675 Cov.: 33 AF XY: 0.896 AC XY: 66734 AN XY: 74486

African (AFR) AF: 0.874 AC: 36291 AN: 41546

American (AMR) AF: 0.902 AC: 13807 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3097 AN: 3472

East Asian (EAS) AF: 0.851 AC: 4409 AN: 5180

South Asian (SAS) AF: 0.913 AC: 4411 AN: 4830

European-Finnish (FIN) AF: 0.972 AC: 10326 AN: 10626

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60492 AN: 68026

Other (OTH) AF: 0.888 AC: 1877 AN: 2114

Alfa AF: 0.889 Hom.: 113799

Bravo AF: 0.888

Asia WGS AF: 0.893 AC: 3105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.50
PhyloP100		-3.0
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: rs2511439; hg19: chr11-67854035;