11-68077412-C-T

Variant names:

• chr11-68077412-C-T
• rs2512612
• NM_001277.3:c.517-2582G>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.517-2582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,898 control chromosomes in the GnomAD database, including 24,443 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 (24443 hom., cov: 31)
• Consequence: CHKA NM_001277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13
• 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKA	NM_001277.3	MANE Select	c.517-2582G>A		intron	N/A	NP_001268.2
	CHKA	NM_001376219.1		c.547-2582G>A		intron	N/A	NP_001363148.1
	CHKA	NM_212469.2		c.463-2582G>A		intron	N/A	NP_997634.1	P35790-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKA	ENST00000265689.9	TSL:1 MANE Select	c.517-2582G>A		intron	N/A	ENSP00000265689.4	P35790-1
	CHKA	ENST00000356135.9	TSL:1	c.463-2582G>A		intron	N/A	ENSP00000348454.4	P35790-2
	CHKA	ENST00000931669.1		c.517-2582G>A		intron	N/A	ENSP00000601728.1

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85858 AN: 151778 Hom.: 24429 Cov.: 31

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.566 AC: 85913 AN: 151898 Hom.: 24443 Cov.: 31 AF XY: 0.571 AC XY: 42377 AN XY: 74262

African (AFR) AF: 0.507 AC: 20967 AN: 41376

American (AMR) AF: 0.658 AC: 10049 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2145 AN: 3468

East Asian (EAS) AF: 0.635 AC: 3282 AN: 5166

South Asian (SAS) AF: 0.685 AC: 3305 AN: 4822

European-Finnish (FIN) AF: 0.585 AC: 6176 AN: 10550

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

European-Non Finnish (NFE) AF: 0.560 AC: 38071 AN: 67934

Other (OTH) AF: 0.589 AC: 1243 AN: 2110

Alfa AF: 0.564 Hom.: 5438

Bravo AF: 0.573

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	-0.96
CADD	Benign	0.051
DANN	Benign	0.30
PhyloP100		-2.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2512612;

hg19: chr11-67844879;