11-68062828-A-G

Variant names:

• chr11-68062828-A-G
• rs7123035
• NM_001277.3:c.1233-794T>C

Variant summary

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

The NM_001277.3(CHKA):​c.1233-794T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 152,230 control chromosomes in the GnomAD database, including 71,267 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 0.97 (71267 hom., cov: 30)
• Consequence: CHKA NM_001277.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00500
• Publications: 1 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHKA	NM_001277.3	c.1233-794T>C		intron_variant	Intron 10 of 11	ENST00000265689.9	NP_001268.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHKA	ENST00000265689.9	c.1233-794T>C		intron_variant	Intron 10 of 11	1	NM_001277.3	ENSP00000265689.4
CHKA	ENST00000356135.9	c.1179-794T>C		intron_variant	Intron 9 of 10	1		ENSP00000348454.4
CHKA	ENST00000525155.5	n.249-794T>C		intron_variant	Intron 3 of 5	5		ENSP00000432631.1

Frequencies

GnomAD3 genomes AF: 0.966 AC: 146991 AN: 152112 Hom.: 71224 Cov.: 30

Gnomad AFR AF: 0.884

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 0.994

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.977

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

GnomAD4 genome AF: 0.966 AC: 147090 AN: 152230 Hom.: 71267 Cov.: 30 AF XY: 0.967 AC XY: 72015 AN XY: 74444

African (AFR) AF: 0.884 AC: 36681 AN: 41490

American (AMR) AF: 0.986 AC: 15079 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.994 AC: 3449 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5183 AN: 5184

South Asian (SAS) AF: 1.00 AC: 4834 AN: 4834

European-Finnish (FIN) AF: 1.00 AC: 10616 AN: 10616

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67988 AN: 68032

Other (OTH) AF: 0.977 AC: 2060 AN: 2108

Alfa AF: 0.965 Hom.: 4930

Bravo AF: 0.961

Asia WGS AF: 0.991 AC: 3447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.9
DANN	Benign	0.30
PhyloP100		0.0050
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: rs7123035; hg19: chr11-67830295;