rs2100944

Variant names:

• chr19-8216751-G-A
• rs2100944
• NM_024552.3:c.-2+5889G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-8216751-G-A
• chr19-8216751-G-C

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+5889G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.804 in 151,954 control chromosomes in the GnomAD database, including 49,494 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 0.80 (49494 hom., cov: 30)
• Consequence: CERS4 NM_024552.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.374
• Publications: 12 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS4	NM_024552.3	c.-2+5889G>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+5889G>A		intron_variant	Intron 2 of 11	1	NM_024552.3	ENSP00000251363.5

Frequencies

GnomAD3 genomes AF: 0.804 AC: 122029 AN: 151836 Hom.: 49438 Cov.: 30

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.804 AC: 122130 AN: 151954 Hom.: 49494 Cov.: 30 AF XY: 0.797 AC XY: 59194 AN XY: 74264

African (AFR) AF: 0.907 AC: 37613 AN: 41486

American (AMR) AF: 0.761 AC: 11582 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2755 AN: 3472

East Asian (EAS) AF: 0.614 AC: 3152 AN: 5136

South Asian (SAS) AF: 0.809 AC: 3888 AN: 4808

European-Finnish (FIN) AF: 0.661 AC: 6964 AN: 10540

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

European-Non Finnish (NFE) AF: 0.787 AC: 53530 AN: 67990

Other (OTH) AF: 0.782 AC: 1643 AN: 2102

Alfa AF: 0.793 Hom.: 113528

Bravo AF: 0.814

Asia WGS AF: 0.667 AC: 2323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.59
PhyloP100		0.37
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: rs2100944; hg19: chr19-8281635;