rs4451553

Positions:

• chr1-150964853-C-T

Variant summary

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

The ENST00000561294.5(CERS2):​c.976-378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 288,790 control chromosomes in the GnomAD database, including 19,359 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 0.34 (9423 hom., cov: 32)
  • Exomes 𝑓: 0.37 (9936 hom.)
• Consequence: CERS2 ENST00000561294.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

Genes affected

CERS2 (HGNC:14076): (ceramide synthase 2) This gene encodes a protein that has sequence similarity to yeast longevity assurance gene 1. Mutation or overexpression of the related gene in yeast has been shown to alter yeast lifespan. The human protein may play a role in the regulation of cell growth. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

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 (SAS) allele frequency at 95% confidence interval = 0.489 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
CERS2	ENST00000561294.5	c.976-378G>A		intron_variant		5		ENSP00000454160
CERS2	ENST00000482825.7	n.969-290G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52411 AN: 151872 Hom.: 9412 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.372 AC: 50882 AN: 136798 Hom.: 9936 AF XY: 0.379 AC XY: 26080 AN XY: 68824

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.505

Gnomad4 ASJ exome AF: 0.399

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.488

Gnomad4 FIN exome AF: 0.349

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.345 AC: 52433 AN: 151992 Hom.: 9423 Cov.: 32 AF XY: 0.351 AC XY: 26062 AN XY: 74294

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.358

Alfa AF: 0.355 Hom.: 4409

Bravo AF: 0.350

Asia WGS AF: 0.426 AC: 1477 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	1.7
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4451553; hg19: chr1-150937329;