dbSNP rs60774903: CERS1:c.-275C>A (chr19-18896790-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001387442.1(CERS1):c.-275C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,398 control chromosomes in the GnomAD database, including 4,839 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 0.21 ( 4838 hom., cov: 32)

Exomes 𝑓: 0.12 ( 1 hom. )

Consequence

CERS1
NM_001387442.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.659

Publications

5 publications found

Variant links:

Genes affected

CERS1 (HGNC:14253): (ceramide synthase 1) This gene encodes a ceramide synthase enzyme, which catalyzes the synthesis of ceramide, the hydrophobic moiety of sphingolipids. The encoded enzyme synthesizes 18-carbon (C18) ceramide in brain neurons. Elevated expression of this gene may be associated with increased longevity, while decreased expression of this gene may be associated with myoclonus epilepsy with dementia in human patients. This protein is transcribed from a monocistronic mRNA as well as a bicistronic mRNA, which also encodes growth differentiation factor 1. [provided by RefSeq, Jul 2016]

CERS1 Gene-Disease associations (from GenCC):

progressive myoclonic epilepsy type 8
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

CERS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
CERS1	NM_001387442.1 link	c.-275C>A	5_prime_UTR_variant	Exon 1 of 7	NP_001374371.1
CERS1	NM_001387443.1 link	c.-110C>A	5_prime_UTR_variant	Exon 1 of 7	NP_001374372.1
CERS1	NM_001290265.2 link	c.-275C>A	5_prime_UTR_variant	Exon 1 of 6	NP_001277194.1	Q5XG75B4DE47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS1	ENST00000542296.6 link	c.-275C>A		upstream_gene_variant		1		ENSP00000437648.1		Q5XG75

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31690

AN:

152064

Hom.:

4837

Cov.:

show subpopulations

Gnomad AFR

AF:

0.432

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.115

Gnomad EAS

AF:

0.0722

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.0621

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.116

AC:

AN:

216

Hom.:

AF XY:

0.117

AC XY:

AN XY:

154

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.116

AC:

AN:

190

Other (OTH)

AF:

0.143

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.208

AC:

31704

AN:

152182

Hom.:

4838

Cov.:

AF XY:

0.201

AC XY:

14965

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.431

AC:

17895

AN:

41490

American (AMR)

AF:

0.145

AC:

2213

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

400

AN:

3472

East Asian (EAS)

AF:

0.0722

AC:

372

AN:

5154

South Asian (SAS)

AF:

0.180

AC:

867

AN:

4826

European-Finnish (FIN)

AF:

0.0621

AC:

660

AN:

10624

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.130

AC:

8861

AN:

68000

Other (OTH)

AF:

0.176

AC:

373

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1181

2362

3543

4724

5905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

318

636

954

1272

1590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.178

Hom.:

440

Bravo

AF:

0.223

Asia WGS

AF:

0.136

AC:

476

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

3.5

(source)

DANN

Benign

0.67

PhyloP100

0.66

PromoterAI

-0.0020

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over