chr11-68100081-C-A

Variant names:

• chr11-68100081-C-A
• rs10791957
• NM_001277.3:c.351-2951G>T

Variant summary

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

The NM_001277.3(CHKA):​c.351-2951G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 152,022 control chromosomes in the GnomAD database, including 22,229 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 0.53 (22229 hom., cov: 33)
• Consequence: CHKA NM_001277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 14 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=-0.88).
• 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.351-2951G>T		intron	N/A	NP_001268.2
	CHKA	NM_001376219.1		c.351-2951G>T		intron	N/A	NP_001363148.1
	CHKA	NM_212469.2		c.351-2951G>T		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.351-2951G>T		intron	N/A	ENSP00000265689.4
	CHKA	ENST00000356135.9	TSL:1	c.351-2951G>T		intron	N/A	ENSP00000348454.4
	CHKA	ENST00000531341.1	TSL:3	c.-16-2951G>T		intron	N/A	ENSP00000435032.1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81089 AN: 151904 Hom.: 22221 Cov.: 33

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.534 AC: 81114 AN: 152022 Hom.: 22229 Cov.: 33 AF XY: 0.539 AC XY: 40071 AN XY: 74282

African (AFR) AF: 0.397 AC: 16458 AN: 41462

American (AMR) AF: 0.645 AC: 9834 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2125 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3279 AN: 5166

South Asian (SAS) AF: 0.685 AC: 3309 AN: 4828

European-Finnish (FIN) AF: 0.586 AC: 6182 AN: 10544

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38066 AN: 67984

Other (OTH) AF: 0.567 AC: 1197 AN: 2110

Alfa AF: 0.564 Hom.: 97750

Bravo AF: 0.536

Asia WGS AF: 0.617 AC: 2144 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.27
PhyloP100		-1.3
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: rs10791957; hg19: chr11-67867548;