Variant 4-84635255-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001263.4(CDS1):c.723-9T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,297,760 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0025 ( 4 hom. )

Consequence

CDS1
NM_001263.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008073

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.07

Variant links:

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]

CDS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 4-84635255-T-A is Benign according to our data. Variant chr4-84635255-T-A is described in ClinVar as [Benign]. Clinvar id is 3049585.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDS1	NM_001263.4 linkuse as main transcript	c.723-9T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000295887.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDS1	ENST00000295887.6 linkuse as main transcript	c.723-9T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001263.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00119

AC:

180

AN:

150680

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000793

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0121

Gnomad FIN

AF:

0.000193

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000695

Gnomad OTH

AF:

0.000974

GnomAD3 exomes

AF:

0.00394

AC:

705

AN:

179016

Hom.:

AF XY:

0.00452

AC XY:

441

AN XY:

97648

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00251

Gnomad ASJ exome

AF:

0.00180

Gnomad EAS exome

AF:

0.00178

Gnomad SAS exome

AF:

0.0156

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00236

Gnomad OTH exome

AF:

0.00389

GnomAD4 exome

AF:

0.00248

AC:

2845

AN:

1146974

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

1565

AN XY:

580164

show subpopulations

Gnomad4 AFR exome

AF:

0.00226

Gnomad4 AMR exome

AF:

0.00201

Gnomad4 ASJ exome

AF:

0.000613

Gnomad4 EAS exome

AF:

0.00277

Gnomad4 SAS exome

AF:

0.0122

Gnomad4 FIN exome

AF:

0.00119

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.00220

GnomAD4 genome

AF:

0.00119

AC:

179

AN:

150786

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

106

AN XY:

73670

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.000792

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.0119

Gnomad4 FIN

AF:

0.000193

Gnomad4 NFE

AF:

0.000695

Gnomad4 OTH

AF:

0.000963

Alfa

AF:

0.00325

Hom.:

Bravo

AF:

0.000967

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CDS1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.33

DANN

Benign

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00081

dbscSNV1_RF

Benign

0.084

SpliceAI score (max)

0.080

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over