chr19-18895857-G-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021267.5(CERS1):c.216C>G(p.Ala72Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,293,584 control chromosomes in the GnomAD database, including 301,065 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 38436 hom., cov: 32)

Exomes 𝑓: 0.67 ( 262629 hom. )

Consequence

CERS1
NM_021267.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.316

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 links:

GDF1 (HGNC:4214): (growth differentiation factor 1) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. Studies in rodents suggest that this protein is involved in the establishment of left-right asymmetry in early embryogenesis and in neural development in later embryogenesis. The encoded protein is translated from a bicistronic mRNA that also encodes ceramide synthase 1. Mutations in this gene are associated with several congenital cardiovascular malformations. [provided by RefSeq, Jul 2016]

GDF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 19-18895857-G-C is Benign according to our data. Variant chr19-18895857-G-C is described in ClinVar as [Benign]. Clinvar id is 402896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.316 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS1	NM_021267.5 link	c.216C>G	p.Ala72Ala	synonymous_variant	Exon 1 of 8	ENST00000623882.4	NP_067090.1	P27544-1
GDF1	NM_001492.6 link	c.-1107C>G		5_prime_UTR_variant	Exon 1 of 8	ENST00000247005.8	NP_001483.3	P27539A0A024R7N8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CERS1	ENST00000623882.4 link	c.216C>G	p.Ala72Ala	synonymous_variant	Exon 1 of 8	1	NM_021267.5	ENSP00000485308.1	P27544-1
CERS1	ENST00000429504.6 link	c.216C>G	p.Ala72Ala	synonymous_variant	Exon 1 of 6	1		ENSP00000389044.1	P27544-2
GDF1	ENST00000247005.8 link	c.-1107C>G		5_prime_UTR_variant	Exon 1 of 8	1	NM_001492.6	ENSP00000247005.5	P27539
CERS1	ENST00000542296.6 link	c.-46+704C>G		intron_variant	Intron 1 of 5	1		ENSP00000437648.1	Q5XG75

Frequencies

GnomAD3 genomes

AF:

0.705

AC:

106516

AN:

151030

Hom.:

38418

Cov.:

show subpopulations

Gnomad AFR

AF:

0.804

Gnomad AMI

AF:

0.606

Gnomad AMR

AF:

0.764

Gnomad ASJ

AF:

0.777

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.543

Gnomad MID

AF:

0.838

Gnomad NFE

AF:

0.690

Gnomad OTH

AF:

0.737

GnomAD3 exomes

AF:

0.570

AC:

9170

AN:

16100

Hom.:

2848

AF XY:

0.564

AC XY:

5811

AN XY:

10306

show subpopulations

Gnomad AFR exome

AF:

0.659

Gnomad AMR exome

AF:

0.647

Gnomad ASJ exome

AF:

0.715

Gnomad EAS exome

AF:

0.243

Gnomad SAS exome

AF:

0.434

Gnomad FIN exome

AF:

0.480

Gnomad NFE exome

AF:

0.631

Gnomad OTH exome

AF:

0.683

GnomAD4 exome

AF:

0.674

AC:

769878

AN:

1142446

Hom.:

262629

Cov.:

AF XY:

0.671

AC XY:

372976

AN XY:

555826

show subpopulations

Gnomad4 AFR exome

AF:

0.801

Gnomad4 AMR exome

AF:

0.742

Gnomad4 ASJ exome

AF:

0.759

Gnomad4 EAS exome

AF:

0.374

Gnomad4 SAS exome

AF:

0.507

Gnomad4 FIN exome

AF:

0.550

Gnomad4 NFE exome

AF:

0.688

Gnomad4 OTH exome

AF:

0.670

GnomAD4 genome

AF:

0.705

AC:

106565

AN:

151138

Hom.:

38436

Cov.:

AF XY:

0.693

AC XY:

51178

AN XY:

73798

show subpopulations

Gnomad4 AFR

AF:

0.803

Gnomad4 AMR

AF:

0.764

Gnomad4 ASJ

AF:

0.777

Gnomad4 EAS

AF:

0.372

Gnomad4 SAS

AF:

0.538

Gnomad4 FIN

AF:

0.543

Gnomad4 NFE

AF:

0.690

Gnomad4 OTH

AF:

0.730

Alfa

AF:

0.691

Hom.:

4584

Bravo

AF:

0.728

Asia WGS

AF:

0.446

AC:

1531

AN:

3432

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Progressive myoclonic epilepsy type 8

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

8.2

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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