19-8262618-T-C

Variant names:

• chr19-8262618-T-C
• rs28133
• ENST00000796540.1:n.855-22533A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000796540.1(ENSG00000303688):​n.855-22533A>G variant causes a intron 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: ENSG00000303688 ENST00000796540.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 7 publications found

Genes affected

ENSG00000303688 (HGNC:):

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

Our verdict: Benign. The variant received -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

African (AFR) AF: 0.881 AC: 36539 AN: 41470

American (AMR) AF: 0.958 AC: 14643 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.957 AC: 3321 AN: 3470

East Asian (EAS) AF: 0.820 AC: 4220 AN: 5148

South Asian (SAS) AF: 0.874 AC: 4213 AN: 4820

European-Finnish (FIN) AF: 0.878 AC: 9297 AN: 10594

Middle Eastern (MID) AF: 0.929 AC: 273 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62694 AN: 67990

Other (OTH) AF: 0.936 AC: 1967 AN: 2102

Alfa AF: 0.922 Hom.: 72540

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
PhyloP100		-2.5

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

Other links and lift over

dbSNP: rs28133; hg19: chr19-8327502;