rs6829806

Variant names:

• chr4-84637687-A-C
• rs6829806
• NM_001263.4:c.811-1237A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001263.4. 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
	CDS1	NM_001263.4	MANE Select	c.811-1237A>C		intron	N/A	NP_001254.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDS1	ENST00000295887.6	TSL:1 MANE Select	c.811-1237A>C		intron	N/A	ENSP00000295887.5

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

African (AFR) AF: 0.439 AC: 18187 AN: 41470

American (AMR) AF: 0.603 AC: 9204 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2263 AN: 3470

East Asian (EAS) AF: 0.630 AC: 3246 AN: 5156

South Asian (SAS) AF: 0.709 AC: 3418 AN: 4820

European-Finnish (FIN) AF: 0.479 AC: 5056 AN: 10552

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39415 AN: 67956

Other (OTH) AF: 0.606 AC: 1273 AN: 2100

Alfa AF: 0.575 Hom.: 70095

Bravo AF: 0.544

Asia WGS AF: 0.681 AC: 2366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.8
DANN	Benign	0.78
PhyloP100		-0.97
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: rs6829806; hg19: chr4-85558840; COSMIC: COSV55688046;