rs10485483

Variant names:

• chr20-5177708-C-A
• rs10485483
• NM_003818.4:c.389+963C>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.389+963C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0896 in 152,148 control chromosomes in the GnomAD database, including 694 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 0.090 (694 hom., cov: 32)
• Consequence: CDS2 NM_003818.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003818.4. 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
	CDS2	NM_003818.4	MANE Select	c.389+963C>A		intron	N/A	NP_003809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDS2	ENST00000460006.6	TSL:1 MANE Select	c.389+963C>A		intron	N/A	ENSP00000419879.1
	CDS2	ENST00000450570.1	TSL:3	c.224+963C>A		intron	N/A	ENSP00000403205.1
	CDS2	ENST00000379070.3	TSL:2	n.644+963C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0896 AC: 13623 AN: 152030 Hom.: 693 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0809

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0214

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0963

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

GnomAD4 genome AF: 0.0896 AC: 13629 AN: 152148 Hom.: 694 Cov.: 32 AF XY: 0.0870 AC XY: 6470 AN XY: 74374

African (AFR) AF: 0.121 AC: 5000 AN: 41476

American (AMR) AF: 0.0809 AC: 1237 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 577 AN: 3466

East Asian (EAS) AF: 0.0215 AC: 111 AN: 5168

South Asian (SAS) AF: 0.135 AC: 651 AN: 4824

European-Finnish (FIN) AF: 0.0367 AC: 389 AN: 10594

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0790 AC: 5376 AN: 68012

Other (OTH) AF: 0.0953 AC: 201 AN: 2110

Alfa AF: 0.0893 Hom.: 993

Bravo AF: 0.0917

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.77
DANN	Benign	0.79
PhyloP100		0.046
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: rs10485483; hg19: chr20-5158354;