Variant rs17159388 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024552.3(CERS4):c.356G>A(p.Arg119Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0331 in 1,612,880 control chromosomes in the GnomAD database, including 2,332 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.074 ( 784 hom., cov: 32)

Exomes 𝑓: 0.029 ( 1548 hom. )

Consequence

CERS4
NM_024552.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.62

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022135377).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS4	NM_024552.3 link	c.356G>A	p.Arg119Gln	missense_variant	5/12	ENST00000251363.10	NP_078828.2	Q9HA82Q53HF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10 link	c.356G>A	p.Arg119Gln	missense_variant	5/12	1	NM_024552.3	ENSP00000251363.5		Q9HA82

Frequencies

GnomAD3 genomes

AF:

0.0740

AC:

11258

AN:

152084

Hom.:

784

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.0308

Gnomad AMR

AF:

0.0485

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.0465

Gnomad FIN

AF:

0.0819

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0167

Gnomad OTH

AF:

0.0703

GnomAD3 exomes

AF:

0.0494

AC:

12260

AN:

247940

Hom.:

650

AF XY:

0.0455

AC XY:

6130

AN XY:

134630

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.0398

Gnomad ASJ exome

AF:

0.00582

Gnomad EAS exome

AF:

0.150

Gnomad SAS exome

AF:

0.0446

Gnomad FIN exome

AF:

0.0780

Gnomad NFE exome

AF:

0.0170

Gnomad OTH exome

AF:

0.0467

GnomAD4 exome

AF:

0.0288

AC:

42133

AN:

1460678

Hom.:

1548

Cov.:

AF XY:

0.0286

AC XY:

20783

AN XY:

726590

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.0424

Gnomad4 ASJ exome

AF:

0.00682

Gnomad4 EAS exome

AF:

0.148

Gnomad4 SAS exome

AF:

0.0421

Gnomad4 FIN exome

AF:

0.0736

Gnomad4 NFE exome

AF:

0.0163

Gnomad4 OTH exome

AF:

0.0400

GnomAD4 genome

AF:

0.0740

AC:

11269

AN:

152202

Hom.:

784

Cov.:

AF XY:

0.0770

AC XY:

5726

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.177

Gnomad4 AMR

AF:

0.0484

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.0453

Gnomad4 FIN

AF:

0.0819

Gnomad4 NFE

AF:

0.0167

Gnomad4 OTH

AF:

0.0691

Alfa

AF:

0.0303

Hom.:

332

Bravo

AF:

0.0789

TwinsUK

AF:

0.0178

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.176

AC:

774

ESP6500EA

AF:

0.0156

AC:

134

ExAC

AF:

0.0502

AC:

6085

Asia WGS

AF:

0.0940

AC:

326

AN:

3478

EpiCase

AF:

0.0164

EpiControl

AF:

0.0157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Uncertain

-0.030

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.82

D;.;D;D;D;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;D;.;D;D;D

MetaRNN

Benign

0.0022

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.88

.;.;L;L;.;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.5

D;D;D;D;D;D

REVEL

Uncertain

0.63

Sift

Uncertain

0.015

D;D;D;D;D;D

Sift4G

Uncertain

0.028

D;D;D;D;T;D

Polyphen

0.98

.;.;D;D;.;.

Vest4

0.27

MPC

0.27

ClinPred

0.042

GERP RS

4.4

Varity_R

0.77

gMVP

0.80

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over