NM_003818.4:c.57+6789G>A

Variant names:

• chr20-5133938-G-A
• rs4239761
• NM_003818.4:c.57+6789G>A

Variant summary

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

The NM_003818.4(CDS2):​c.57+6789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.865 in 152,262 control chromosomes in the GnomAD database, including 57,456 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 0.86 (57456 hom., cov: 33)
• Consequence: CDS2 NM_003818.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 9 publications found

Genes affected

CDS2 (HGNC:1801): (CDP-diacylglycerol synthase 2) 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDS2	NM_003818.4	c.57+6789G>A		intron_variant	Intron 1 of 12	ENST00000460006.6	NP_003809.1
CDS2	XM_006723660.3	c.57+6789G>A		intron_variant	Intron 1 of 11		XP_006723723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDS2	ENST00000460006.6	c.57+6789G>A		intron_variant	Intron 1 of 12	1	NM_003818.4	ENSP00000419879.1

Frequencies

GnomAD3 genomes AF: 0.865 AC: 131530 AN: 152144 Hom.: 57400 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.866

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.876

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

GnomAD4 genome AF: 0.865 AC: 131646 AN: 152262 Hom.: 57456 Cov.: 33 AF XY: 0.864 AC XY: 64296 AN XY: 74418

African (AFR) AF: 0.968 AC: 40245 AN: 41566

American (AMR) AF: 0.883 AC: 13504 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.866 AC: 3005 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5182 AN: 5188

South Asian (SAS) AF: 0.899 AC: 4331 AN: 4818

European-Finnish (FIN) AF: 0.746 AC: 7893 AN: 10574

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54654 AN: 68028

Other (OTH) AF: 0.878 AC: 1857 AN: 2116

Alfa AF: 0.833 Hom.: 37133

Bravo AF: 0.882

Asia WGS AF: 0.951 AC: 3308 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.0
DANN	Benign	0.41
PhyloP100		-0.13
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: rs4239761; hg19: chr20-5114584;