rs1910412

Positions:

• chr15-100540007-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+4644T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 151,984 control chromosomes in the GnomAD database, including 20,451 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 0.52 (20451 hom., cov: 32)
• Consequence: CERS3 ENST00000284382.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS3	NM_001290341.2	c.-461+4209T>G		intron_variant
CERS3	NM_001290342.2	c.-355+4117T>G		intron_variant
CERS3	NM_001290343.2	c.-355+4640T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS3	ENST00000284382.8	c.-355+4644T>G		intron_variant		1		P1
CERS3	ENST00000394113.5	c.-494+4209T>G		intron_variant		1		P1
CERS3	ENST00000538112.6	c.-355+4117T>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78312 AN: 151864 Hom.: 20434 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.516 AC: 78378 AN: 151984 Hom.: 20451 Cov.: 32 AF XY: 0.521 AC XY: 38738 AN XY: 74292

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.514

Alfa AF: 0.520 Hom.: 26625

Bravo AF: 0.508

Asia WGS AF: 0.483 AC: 1681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.52
DANN	Benign	0.65

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: rs1910412; hg19: chr15-101080212;