Variant 15-100455833-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001378789.1(CERS3):c.999+60G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 1,074,012 control chromosomes in the GnomAD database, including 246,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.69 ( 36053 hom., cov: 32)

Exomes 𝑓: 0.67 ( 210884 hom. )

Consequence

CERS3
NM_001378789.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0630

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 15-100455833-C-T is Benign according to our data. Variant chr15-100455833-C-T is described in ClinVar as [Benign]. Clinvar id is 1209731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERS3	NM_001378789.1 linkuse as main transcript	c.999+60G>A		intron_variant		ENST00000679737.1	NP_001365718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERS3	ENST00000679737.1 linkuse as main transcript	c.999+60G>A		intron_variant			NM_001378789.1	ENSP00000506641	P1

Frequencies

GnomAD3 genomes

AF:

0.689

AC:

104339

AN:

151420

Hom.:

36020

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.622

Gnomad AMR

AF:

0.772

Gnomad ASJ

AF:

0.666

Gnomad EAS

AF:

0.580

Gnomad SAS

AF:

0.590

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.661

Gnomad NFE

AF:

0.678

Gnomad OTH

AF:

0.692

GnomAD4 exome

AF:

0.674

AC:

621732

AN:

922474

Hom.:

210884

AF XY:

0.670

AC XY:

312897

AN XY:

467172

show subpopulations

Gnomad4 AFR exome

AF:

0.706

Gnomad4 AMR exome

AF:

0.805

Gnomad4 ASJ exome

AF:

0.663

Gnomad4 EAS exome

AF:

0.591

Gnomad4 SAS exome

AF:

0.561

Gnomad4 FIN exome

AF:

0.686

Gnomad4 NFE exome

AF:

0.680

Gnomad4 OTH exome

AF:

0.668

GnomAD4 genome

AF:

0.689

AC:

104422

AN:

151538

Hom.:

36053

Cov.:

AF XY:

0.689

AC XY:

51015

AN XY:

74002

show subpopulations

Gnomad4 AFR

AF:

0.700

Gnomad4 AMR

AF:

0.772

Gnomad4 ASJ

AF:

0.666

Gnomad4 EAS

AF:

0.580

Gnomad4 SAS

AF:

0.590

Gnomad4 FIN

AF:

0.710

Gnomad4 NFE

AF:

0.678

Gnomad4 OTH

AF:

0.688

Alfa

AF:

0.685

Hom.:

9041

Bravo

AF:

0.695

Asia WGS

AF:

0.586

AC:

2039

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Autosomal recessive congenital ichthyosis 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.67

DANN

Benign

0.34

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over