rs12438080

Positions:

• chr15-100541858-A-C

Variant summary

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

The ENST00000284382.8(CERS3):​c.-355+2793T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,832 control chromosomes in the GnomAD database, including 19,249 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 0.50 (19249 hom., cov: 33)
• Consequence: CERS3 ENST00000284382.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823

Genes affected

CERS3 (HGNC:23752): (ceramide synthase 3) This gene is a member of the ceramide synthase family of genes. The ceramide synthase enzymes regulate sphingolipid synthesis by catalyzing the formation of ceramides from sphingoid base and acyl-coA substrates. This family member is involved in the synthesis of ceramides with ultra-long-chain acyl moieties (ULC-Cers), important to the epidermis in its role in creating a protective barrier from the environment. The protein encoded by this gene has also been implicated in modification of the lipid structures required for spermatogenesis. Mutations in this gene have been associated with male fertility defects, and epidermal defects, including ichthyosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS3	NM_001290341.2	c.-461+2358T>G		intron_variant
CERS3	NM_001290342.2	c.-355+2266T>G		intron_variant
CERS3	NM_001290343.2	c.-355+2789T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS3	ENST00000284382.8	c.-355+2793T>G		intron_variant		1		P1
CERS3	ENST00000394113.5	c.-494+2358T>G		intron_variant		1		P1
CERS3	ENST00000538112.6	c.-355+2266T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75801 AN: 151712 Hom.: 19233 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.500 AC: 75865 AN: 151832 Hom.: 19249 Cov.: 33 AF XY: 0.505 AC XY: 37504 AN XY: 74196

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.500

Alfa AF: 0.510 Hom.: 4608

Bravo AF: 0.491

Asia WGS AF: 0.475 AC: 1650 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.52

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: rs12438080; hg19: chr15-101082063;