rs1466448

Variant names:

• chr19-8224635-C-A
• rs1466448
• NM_024552.3:c.-2+13773C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-8224635-C-A
• chr19-8224635-C-G
• chr19-8224635-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000271717 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CERS4	NM_024552.3	c.-2+13773C>A		intron_variant	Intron 2 of 11	ENST00000251363.10	NP_078828.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000251363.10	c.-2+13773C>A		intron_variant	Intron 2 of 11	1	NM_024552.3	ENSP00000251363.5

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

African (AFR) AF: 0.908 AC: 37702 AN: 41526

American (AMR) AF: 0.769 AC: 11724 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.787 AC: 2732 AN: 3472

East Asian (EAS) AF: 0.798 AC: 4109 AN: 5146

South Asian (SAS) AF: 0.795 AC: 3833 AN: 4820

European-Finnish (FIN) AF: 0.737 AC: 7775 AN: 10550

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54136 AN: 67990

Other (OTH) AF: 0.802 AC: 1692 AN: 2110

Alfa AF: 0.805 Hom.: 205925

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
PhyloP100		-3.1
PromoterAI		-0.0088	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs1466448; hg19: chr19-8289519;