rs8029244

Variant names:

• chr15-100468370-A-C
• rs8029244
• NM_001378789.1:c.845+1008T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-100468370-A-C
• chr15-100468370-A-G
• chr15-100468370-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001378789.1(CERS3):​c.845+1008T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,922 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 31)
• Consequence: CERS3 NM_001378789.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378789.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS3	NM_001378789.1	MANE Select	c.845+1008T>G		intron	N/A	NP_001365718.1
	CERS3	NM_001290341.2		c.878+1008T>G		intron	N/A	NP_001277270.1
	CERS3	NM_001290342.2		c.845+1008T>G		intron	N/A	NP_001277271.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERS3	ENST00000679737.1	MANE Select	c.845+1008T>G		intron	N/A	ENSP00000506641.1
	CERS3	ENST00000284382.8	TSL:1	c.845+1008T>G		intron	N/A	ENSP00000284382.4
	CERS3	ENST00000394113.5	TSL:1	c.845+1008T>G		intron	N/A	ENSP00000377672.3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151922 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151922 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74184

African (AFR) AF: 0.00 AC: 0 AN: 41372

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67972

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.00 Hom.: 5989

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.36
DANN	Benign	0.39
PhyloP100		-0.83

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: rs8029244; hg19: chr15-101008575;