rs11881630

chr19-8254571-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_024552.3(CERS4):c.246C>T(p.Ala82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,613,086 control chromosomes in the GnomAD database, including 2,362 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.

• Frequency:
  • Genomes: 𝑓 0.075 (799 hom., cov: 31)
  • Exomes 𝑓: 0.029 (1563 hom.)
• Consequence: CERS4 NM_024552.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-0.995 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS4	NM_024552.3	c.246C>T	p.Ala82=	synonymous_variant	4/12	ENST00000251363.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS4	ENST00000251363.10	c.246C>T	p.Ala82=	synonymous_variant	4/12	1	NM_024552.3	P1

Frequencies

GnomAD3 genomes AF: 0.0750 AC: 11412 AN: 152108 Hom.: 799 Cov.: 31

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0816

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0170

Gnomad OTH AF: 0.0686

GnomAD3 exomes AF: 0.0493 AC: 12291 AN: 249306 Hom.: 645 AF XY: 0.0454 AC XY: 6119 AN XY: 134796

Gnomad AFR exome AF: 0.184

Gnomad AMR exome AF: 0.0396

Gnomad ASJ exome AF: 0.00589

Gnomad EAS exome AF: 0.148

Gnomad SAS exome AF: 0.0445

Gnomad FIN exome AF: 0.0769

Gnomad NFE exome AF: 0.0170

Gnomad OTH exome AF: 0.0466

GnomAD4 exome AF: 0.0289 AC: 42232 AN: 1460860 Hom.: 1563 Cov.: 31 AF XY: 0.0287 AC XY: 20835 AN XY: 726676

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.0422

Gnomad4 ASJ exome AF: 0.00685

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.0420

Gnomad4 FIN exome AF: 0.0728

Gnomad4 NFE exome AF: 0.0163

Gnomad4 OTH exome AF: 0.0402

GnomAD4 genome AF: 0.0751 AC: 11428 AN: 152226 Hom.: 799 Cov.: 31 AF XY: 0.0779 AC XY: 5797 AN XY: 74436

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0486

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.0816

Gnomad4 NFE AF: 0.0170

Gnomad4 OTH AF: 0.0674

Alfa AF: 0.0388 Hom.: 153

Bravo AF: 0.0802

Asia WGS AF: 0.0950 AC: 329 AN: 3478

EpiCase AF: 0.0165

EpiControl AF: 0.0156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.6
Dann	Benign	0.46

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: rs11881630; hg19: chr19-8319455; COSMIC: COSV52167030; COSMIC: COSV52167030;