rs7258249

Positions:

• chr19-8206837-G-A

Variant summary

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

The ENST00000561008.5(CERS4):​c.-191+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 155,618 control chromosomes in the GnomAD database, including 12,144 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 0.37 (11852 hom., cov: 29)
  • Exomes 𝑓: 0.34 (292 hom.)
• Consequence: CERS4 ENST00000561008.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS4	ENST00000561008.5	c.-191+38G>A		intron_variant		4		ENSP00000453796

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55822 AN: 151492 Hom.: 11848 Cov.: 29

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.391

GnomAD4 exome AF: 0.344 AC: 1378 AN: 4008 Hom.: 292 Cov.: 0 AF XY: 0.343 AC XY: 713 AN XY: 2078

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.412

Gnomad4 EAS exome AF: 0.0528

Gnomad4 SAS exome AF: 0.339

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.368 AC: 55845 AN: 151610 Hom.: 11852 Cov.: 29 AF XY: 0.361 AC XY: 26757 AN XY: 74028

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.0561

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.386

Alfa AF: 0.465 Hom.: 17054

Bravo AF: 0.356

Asia WGS AF: 0.184 AC: 642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.0
DANN	Benign	0.59

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: rs7258249; hg19: chr19-8271721;