Genetic Variant CERS5:n.*2004A>G (chr12-50130181-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000380189.8(CERS5):n.*2004A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 176,074 control chromosomes in the GnomAD database, including 45,023 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 0.71 ( 39775 hom., cov: 31)

Exomes 𝑓: 0.65 ( 5248 hom. )

Consequence

CERS5
ENST00000380189.8 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.682

Publications

18 publications found

Variant links:

Genes affected

CERS5 (HGNC:23749): (ceramide synthase 5) This gene encodes a protein that belongs to the TLC (TRAM, LAG1 and CLN8 homology domains) family of proteins. The encoded protein functions in the synthesis of ceramide, a lipid molecule that is involved in a several cellular signaling pathways. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

CERS5 links:

ENSG00000272368 (HGNC:):

ENSG00000272368 links:

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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=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERS5	NM_147190.5 link	c.*364A>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000317551.12	NP_671723.1	Q8N5B7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERS5	ENST00000317551.12 link	c.*364A>G		3_prime_UTR_variant	Exon 10 of 10	2	NM_147190.5	ENSP00000325485.6		Q8N5B7-1

Frequencies

GnomAD3 genomes

AF:

0.712

AC:

108132

AN:

151956

Hom.:

39725

Cov.:

show subpopulations

Gnomad AFR

AF:

0.882

Gnomad AMI

AF:

0.568

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.525

Gnomad EAS

AF:

0.918

Gnomad SAS

AF:

0.779

Gnomad FIN

AF:

0.609

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.682

GnomAD4 exome

AF:

0.652

AC:

15650

AN:

24000

Hom.:

5248

Cov.:

AF XY:

0.647

AC XY:

8031

AN XY:

12420

show subpopulations

African (AFR)

AF:

0.890

AC:

739

AN:

830

American (AMR)

AF:

0.681

AC:

830

AN:

1218

Ashkenazi Jewish (ASJ)

AF:

0.515

AC:

460

AN:

894

East Asian (EAS)

AF:

0.919

AC:

1163

AN:

1266

South Asian (SAS)

AF:

0.751

AC:

536

AN:

714

European-Finnish (FIN)

AF:

0.638

AC:

1000

AN:

1568

Middle Eastern (MID)

AF:

0.545

AC:

AN:

112

European-Non Finnish (NFE)

AF:

0.622

AC:

9828

AN:

15812

Other (OTH)

AF:

0.651

AC:

1033

AN:

1586

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

266

531

797

1062

1328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.712

AC:

108236

AN:

152074

Hom.:

39775

Cov.:

AF XY:

0.712

AC XY:

52928

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.882

AC:

36602

AN:

41500

American (AMR)

AF:

0.680

AC:

10379

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.525

AC:

1819

AN:

3468

East Asian (EAS)

AF:

0.918

AC:

4747

AN:

5170

South Asian (SAS)

AF:

0.778

AC:

3755

AN:

4826

European-Finnish (FIN)

AF:

0.609

AC:

6429

AN:

10556

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.624

AC:

42376

AN:

67964

Other (OTH)

AF:

0.682

AC:

1443

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1485

2970

4456

5941

7426

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.642

Hom.:

55491

Bravo

AF:

0.723

Asia WGS

AF:

0.824

AC:

2864

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.7

(source)

DANN

Benign

0.58

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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