rs6829806

Positions:

• chr4-84637687-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001263.4(CDS1):​c.811-1237A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,996 control chromosomes in the GnomAD database, including 22,880 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 0.54 (22880 hom., cov: 32)
• Consequence: CDS1 NM_001263.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.972

Genes affected

CDS1 (HGNC:1800): (CDP-diacylglycerol synthase 1) Breakdown products of phosphoinositides are ubiquitous second messengers that function downstream of many G protein-coupled receptors and tyrosine kinases regulating cell growth, calcium metabolism, and protein kinase C activity. This gene encodes an enzyme which regulates the amount of phosphatidylinositol available for signaling by catalyzing the conversion of phosphatidic acid to CDP-diacylglycerol. This enzyme is an integral membrane protein localized to two subcellular domains, the matrix side of the inner mitochondrial membrane where it is thought to be involved in the synthesis of phosphatidylglycerol and cardiolipin and the cytoplasmic side of the endoplasmic reticulum where it functions in phosphatidylinositol biosynthesis. Two genes encoding this enzyme have been identified in humans, one mapping to human chromosome 4q21 and a second to 20p13. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDS1	NM_001263.4	c.811-1237A>C		intron_variant		ENST00000295887.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDS1	ENST00000295887.6	c.811-1237A>C		intron_variant		1	NM_001263.4	P1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82589 AN: 151876 Hom.: 22862 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.544 AC: 82653 AN: 151996 Hom.: 22880 Cov.: 32 AF XY: 0.543 AC XY: 40290 AN XY: 74252

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.606

Alfa AF: 0.588 Hom.: 43387

Bravo AF: 0.544

Asia WGS AF: 0.681 AC: 2366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.78

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

Publications

LitVar

Other links and lift over

dbSNP: rs6829806; hg19: chr4-85558840; COSMIC: COSV55688046;