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GeneBe

12-50167136-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_147190.5(CERS5):c.162G>A(p.Ala54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,577,306 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00067 ( 5 hom. )

Consequence

CERS5
NM_147190.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0240
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-50167136-C-T is Benign according to our data. Variant chr12-50167136-C-T is described in ClinVar as [Benign]. Clinvar id is 768542.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.024 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0069 (1051/152234) while in subpopulation AFR AF= 0.0237 (985/41566). AF 95% confidence interval is 0.0225. There are 6 homozygotes in gnomad4. There are 474 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CERS5NM_147190.5 linkuse as main transcriptc.162G>A p.Ala54= synonymous_variant 1/10 ENST00000317551.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CERS5ENST00000317551.12 linkuse as main transcriptc.162G>A p.Ala54= synonymous_variant 1/102 NM_147190.5 P1Q8N5B7-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00687
AC:
1045
AN:
152118
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0236
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00321
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00669
GnomAD3 exomes
AF:
0.00120
AC:
223
AN:
185804
Hom.:
3
AF XY:
0.000836
AC XY:
87
AN XY:
104102
show subpopulations
Gnomad AFR exome
AF:
0.0211
Gnomad AMR exome
AF:
0.00108
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000620
GnomAD4 exome
AF:
0.000672
AC:
957
AN:
1425072
Hom.:
5
Cov.:
31
AF XY:
0.000548
AC XY:
388
AN XY:
707838
show subpopulations
Gnomad4 AFR exome
AF:
0.0243
Gnomad4 AMR exome
AF:
0.00129
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000240
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000291
Gnomad4 OTH exome
AF:
0.00175
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00690
AC:
1051
AN:
152234
Hom.:
6
Cov.:
32
AF XY:
0.00637
AC XY:
474
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0237
Gnomad4 AMR
AF:
0.00320
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00662
Alfa
AF:
0.00208
Hom.:
0
Bravo
AF:
0.00804
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeNov 20, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.45
Cadd
Benign
13
Dann
Benign
0.95
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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.

Other links and lift over

dbSNP: rs79554344; hg19: chr12-50560919; API