Variant 4-84635256-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001263.4(CDS1):c.723-8A>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,358,350 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.020 ( 78 hom., cov: 31)

Exomes 𝑓: 0.0020 ( 11 hom. )

Consequence

CDS1
NM_001263.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001159

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 4-84635256-A-T is Benign according to our data. Variant chr4-84635256-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 775994.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDS1	NM_001263.4 linkuse as main transcript	c.723-8A>T		splice_region_variant, 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.723-8A>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001263.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2886

AN:

147490

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0667

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000592

Gnomad SAS

AF:

0.000641

Gnomad FIN

AF:

0.000426

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.00985

GnomAD3 exomes

AF:

0.00489

AC:

895

AN:

182854

Hom.:

AF XY:

0.00366

AC XY:

369

AN XY:

100910

show subpopulations

Gnomad AFR exome

AF:

0.0514

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.000620

Gnomad EAS exome

AF:

0.000618

Gnomad SAS exome

AF:

0.000600

Gnomad FIN exome

AF:

0.00136

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00345

GnomAD4 exome

AF:

0.00205

AC:

2477

AN:

1210764

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

1192

AN XY:

610430

show subpopulations

Gnomad4 AFR exome

AF:

0.0503

Gnomad4 AMR exome

AF:

0.00370

Gnomad4 ASJ exome

AF:

0.0000924

Gnomad4 EAS exome

AF:

0.000299

Gnomad4 SAS exome

AF:

0.000583

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.000855

Gnomad4 OTH exome

AF:

0.00367

GnomAD4 genome

AF:

0.0196

AC:

2890

AN:

147586

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1394

AN XY:

71774

show subpopulations

Gnomad4 AFR

AF:

0.0666

Gnomad4 AMR

AF:

0.00634

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000594

Gnomad4 SAS

AF:

0.000643

Gnomad4 FIN

AF:

0.000426

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.00975

Alfa

AF:

0.00664

Hom.:

Bravo

AF:

0.0213

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.55

DANN

Benign

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.014

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

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