rs17159388

Positions:

• chr19-8255671-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.074 (784 hom., cov: 32)
  • Exomes 𝑓: 0.029 (1548 hom.)
• Consequence: CERS4 NM_024552.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

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 (HGNC:):

ACMG classification

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	c.356G>A	p.Arg119Gln	missense_variant	5/12	ENST00000251363.10	NP_078828.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0740 AC: 11258 AN: 152084 Hom.: 784 Cov.: 32

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

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.: 34 AF XY: 0.0286 AC XY: 20783 AN XY: 726590

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.: 32 AF XY: 0.0770 AC XY: 5726 AN XY: 74404

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: 66

ALSPAC AF: 0.0143 AC: 55

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	T
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	26
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	D
LIST_S2	Uncertain	0.93	D;D;.;D;D;D
MetaRNN	Benign	0.0022	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	.;.;L;L;.;.
PrimateAI	Benign	0.43	T
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	T
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

Other links and lift over

dbSNP: rs17159388; hg19: chr19-8320555; COSMIC: COSV52165795; COSMIC: COSV52165795;