Variant 5-75385948-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379029.1(CERT1):c.1371A>G(p.Glu457=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,586,116 control chromosomes in the GnomAD database, including 43,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4357 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39574 hom. )

Consequence

CERT1
NM_001379029.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.497

Variant links:

Genes affected

CERT1 (HGNC:2205): (ceramide transporter 1) This gene encodes a kinase that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture disease is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CERT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 5-75385948-T-C is Benign according to our data. Variant chr5-75385948-T-C is described in ClinVar as [Benign]. Clinvar id is 1275144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.497 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERT1	NM_001379029.1 linkuse as main transcript	c.1371A>G	p.Glu457=	synonymous_variant	13/17	ENST00000643780.2	NP_001365958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000643780.2 linkuse as main transcript	c.1371A>G	p.Glu457=	synonymous_variant	13/17		NM_001379029.1	ENSP00000495760	P3	Q9Y5P4-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

35691

AN:

152068

Hom.:

4351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.281

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.280

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.227

GnomAD3 exomes

AF:

0.240

AC:

56716

AN:

236308

Hom.:

7684

AF XY:

0.250

AC XY:

31995

AN XY:

127988

show subpopulations

Gnomad AFR exome

AF:

0.253

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.277

Gnomad EAS exome

AF:

0.317

Gnomad SAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.227

AC:

325513

AN:

1433930

Hom.:

39574

Cov.:

AF XY:

0.233

AC XY:

165722

AN XY:

712372

show subpopulations

Gnomad4 AFR exome

AF:

0.263

Gnomad4 AMR exome

AF:

0.146

Gnomad4 ASJ exome

AF:

0.279

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.231

GnomAD4 genome

AF:

0.235

AC:

35724

AN:

152186

Hom.:

4357

Cov.:

AF XY:

0.240

AC XY:

17858

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.258

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.280

Gnomad4 EAS

AF:

0.324

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.219

Hom.:

7103

Bravo

AF:

0.227

Asia WGS

AF:

0.356

AC:

1237

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2019	- -

CERT1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

-0.52

CADD

Benign

6.6

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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