Variant 19-8256678-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_024552.3(CERS4):c.580C>T(p.Leu194=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,613,894 control chromosomes in the GnomAD database, including 246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0067 ( 40 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 206 hom. )

Consequence

CERS4
NM_024552.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.353

Variant links:

Genes affected

CERS4 (HGNC:23747): (ceramide synthase 4) Enables sphingosine N-acyltransferase activity. Involved in ceramide biosynthetic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

CERS4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 19-8256678-C-T is Benign according to our data. Variant chr19-8256678-C-T is described in ClinVar as [Benign]. Clinvar id is 770654.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.353 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS4	NM_024552.3 linkuse as main transcript	c.580C>T	p.Leu194=	synonymous_variant	8/12	ENST00000251363.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS4	ENST00000251363.10 linkuse as main transcript	c.580C>T	p.Leu194=	synonymous_variant	8/12	1	NM_024552.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00667

AC:

1015

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00150

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0270

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0884

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.00949

AC:

2382

AN:

250958

Hom.:

AF XY:

0.00841

AC XY:

1141

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0834

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000326

Gnomad OTH exome

AF:

0.00900

GnomAD4 exome

AF:

0.00380

AC:

5553

AN:

1461576

Hom.:

206

Cov.:

AF XY:

0.00361

AC XY:

2622

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0212

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0908

Gnomad4 SAS exome

AF:

0.00181

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000189

Gnomad4 OTH exome

AF:

0.00974

GnomAD4 genome

AF:

0.00669

AC:

1019

AN:

152318

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

549

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.0269

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0886

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00875

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

8.3

DANN

Benign

0.65

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

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