rs1910412

Variant names:

• chr15-100540007-A-C
• rs1910412
• ENST00000284382.8:c.-355+4644T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 9

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• congenital non-bullous ichthyosiform erythroderma

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CERS3	NM_001290341.2	c.-461+4209T>G		intron_variant	Intron 1 of 13		NP_001277270.1
CERS3	NM_001290342.2	c.-355+4117T>G		intron_variant	Intron 1 of 12		NP_001277271.1
CERS3	NM_001290343.2	c.-355+4640T>G		intron_variant	Intron 1 of 12		NP_001277272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS3	ENST00000284382.8	c.-355+4644T>G		intron_variant	Intron 1 of 12	1		ENSP00000284382.4
CERS3	ENST00000394113.5	c.-494+4209T>G		intron_variant	Intron 1 of 13	1		ENSP00000377672.3
CERS3	ENST00000538112.6	c.-355+4117T>G		intron_variant	Intron 1 of 12	1		ENSP00000437640.2

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

African (AFR) AF: 0.489 AC: 20277 AN: 41438

American (AMR) AF: 0.583 AC: 8902 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1562 AN: 3464

East Asian (EAS) AF: 0.306 AC: 1576 AN: 5158

South Asian (SAS) AF: 0.596 AC: 2874 AN: 4822

European-Finnish (FIN) AF: 0.590 AC: 6222 AN: 10552

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.519 AC: 35300 AN: 67966

Other (OTH) AF: 0.514 AC: 1085 AN: 2110

Alfa AF: 0.517 Hom.: 70819

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
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1910412; hg19: chr15-101080212;