rs60774903

Positions:

• chr19-18896790-G-T

Variant summary

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

The NM_001387442.1(CERS1):​c.-275C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,398 control chromosomes in the GnomAD database, including 4,839 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 0.21 (4838 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: CERS1 NM_001387442.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.659

Genes affected

CERS1 (HGNC:14253): (ceramide synthase 1) This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS1	NM_001387442.1	c.-275C>A		5_prime_UTR_variant	1/7		NP_001374371.1
CERS1	NM_001387443.1	c.-110C>A		5_prime_UTR_variant	1/7		NP_001374372.1
CERS1	NM_001290265.2	c.-275C>A		5_prime_UTR_variant	1/6		NP_001277194.1
		n.18896790G>T		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31690 AN: 152064 Hom.: 4837 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.145

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0722

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0621

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.116 AC: 25 AN: 216 Hom.: 1 AF XY: 0.117 AC XY: 18 AN XY: 154

Gnomad4 AFR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.116

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.208 AC: 31704 AN: 152182 Hom.: 4838 Cov.: 32 AF XY: 0.201 AC XY: 14965 AN XY: 74400

Gnomad4 AFR AF: 0.431

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0722

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.0621

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.176

Alfa AF: 0.178 Hom.: 440

Bravo AF: 0.223

Asia WGS AF: 0.136 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs60774903; hg19: chr19-19007599;