19-8262618-T-C

Variant names:

• chr19-8262618-T-C
• rs28133
• NM_024552.3:c.*509T>C

Variant summary

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

The NM_024552.3(CERS4):​c.*509T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,080 control chromosomes in the GnomAD database, including 62,717 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 0.91 (62717 hom., cov: 30)
• Consequence: CERS4 NM_024552.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS4	NM_024552.3	c.*509T>C		downstream_gene_variant		ENST00000251363.10	NP_078828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10	c.*509T>C		downstream_gene_variant		1	NM_024552.3	ENSP00000251363.5

Frequencies

GnomAD3 genomes AF: 0.908 AC: 137944 AN: 151960 Hom.: 62670 Cov.: 30

Gnomad AFR AF: 0.881

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.957

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.878

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.935

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.908 AC: 138048 AN: 152080 Hom.: 62717 Cov.: 30 AF XY: 0.906 AC XY: 67331 AN XY: 74352

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.958

Gnomad4 ASJ AF: 0.957

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.878

Gnomad4 NFE AF: 0.922

Gnomad4 OTH AF: 0.936

Alfa AF: 0.922 Hom.: 62664

Bravo AF: 0.914

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.074
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: rs28133; hg19: chr19-8327502;