rs1466448

chr19-8224635-C-A

Variant summary

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

The NM_024552.3(CERS4):c.-2+13773C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,058 control chromosomes in the GnomAD database, including 51,358 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 0.82 (51358 hom., cov: 31)
• Consequence: CERS4 NM_024552.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS4	NM_024552.3	c.-2+13773C>A		intron_variant		ENST00000251363.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS4	ENST00000251363.10	c.-2+13773C>A		intron_variant		1	NM_024552.3	P1
	ENST00000605980.1	n.292-2426G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124612 AN: 151940 Hom.: 51310 Cov.: 31

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.787

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.820 AC: 124708 AN: 152058 Hom.: 51358 Cov.: 31 AF XY: 0.816 AC XY: 60669 AN XY: 74310

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.769

Gnomad4 ASJ AF: 0.787

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.795

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.802

Alfa AF: 0.799 Hom.: 95282

Bravo AF: 0.826

Asia WGS AF: 0.741 AC: 2578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.33
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs1466448; hg19: chr19-8289519;