19-8220846-G-C

Variant names:

• chr19-8220846-G-C
• rs11666913
• NM_024552.3:c.-2+9984G>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+9984G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 150,418 control chromosomes in the GnomAD database, including 7,847 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 0.30 (7847 hom., cov: 28)
• Consequence: CERS4 NM_024552.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS4	NM_024552.3	c.-2+9984G>C		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+9984G>C		intron_variant	Intron 2 of 11	1	NM_024552.3	ENSP00000251363.5

Frequencies

GnomAD3 genomes AF: 0.297 AC: 44636 AN: 150304 Hom.: 7847 Cov.: 28

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.0513

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.297 AC: 44647 AN: 150418 Hom.: 7847 Cov.: 28 AF XY: 0.289 AC XY: 21195 AN XY: 73344

African (AFR) AF: 0.144 AC: 5939 AN: 41118

American (AMR) AF: 0.271 AC: 4086 AN: 15058

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1341 AN: 3466

East Asian (EAS) AF: 0.0514 AC: 263 AN: 5114

South Asian (SAS) AF: 0.266 AC: 1265 AN: 4754

European-Finnish (FIN) AF: 0.284 AC: 2862 AN: 10080

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.412 AC: 27837 AN: 67552

Other (OTH) AF: 0.318 AC: 662 AN: 2080

Alfa AF: 0.324 Hom.: 1110

Bravo AF: 0.290

Asia WGS AF: 0.140 AC: 487 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.6
DANN	Benign	0.58
PhyloP100		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs11666913; hg19: chr19-8285730;