15-100434110-T-C

Position:

• chr15-100434110-T-C

Variant summary

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

The NM_001378789.1(CERS3):​c.999+21783A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.836 in 152,260 control chromosomes in the GnomAD database, including 53,601 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 0.84 (53601 hom., cov: 34)
• Consequence: CERS3 NM_001378789.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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]

CERS3-AS1 (HGNC:51431): (CERS3 antisense RNA 1)

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 (NFE) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERS3	NM_001378789.1	c.999+21783A>G		intron_variant		ENST00000679737.1
CERS3-AS1	NR_120374.1	n.396-3668T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERS3	ENST00000679737.1	c.999+21783A>G		intron_variant			NM_001378789.1	P1
CERS3-AS1	ENST00000560643.1	n.236-3668T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127200 AN: 152142 Hom.: 53585 Cov.: 34

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.836 AC: 127269 AN: 152260 Hom.: 53601 Cov.: 34 AF XY: 0.833 AC XY: 62023 AN XY: 74462

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.838

Gnomad4 NFE AF: 0.891

Gnomad4 OTH AF: 0.876

Alfa AF: 0.865 Hom.: 29588

Bravo AF: 0.827

Asia WGS AF: 0.880 AC: 3060 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	2.4
DANN	Benign	0.53

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: rs1966764; hg19: chr15-100974315;