5-75374198-GA-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_001130105.1(CERT1):​c.*10-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 293,662 control chromosomes in the GnomAD database, including 75 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.039 ( 74 hom., cov: 29)
Exomes 𝑓: 0.22 ( 1 hom. )

Consequence

CERT1
NM_001130105.1 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.108
Variant links:
Genes affected
CERT1 (HGNC:2205): (ceramide transporter 1) This gene encodes a kinase that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture disease is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6
Variant 5-75374198-GA-G is Benign according to our data. Variant chr5-75374198-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1206283.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-75374198-GA-G is described in Lovd as [Benign]. Variant chr5-75374198-GA-G is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CERT1NM_001130105.1 linkuse as main transcriptc.*10-8delT splice_region_variant, intron_variant NP_001123577.1 Q9Y5P4-3
CERT1NM_001379002.1 linkuse as main transcriptc.*9+5138delT intron_variant NP_001365931.1
CERT1NM_005713.3 linkuse as main transcriptc.*10-8delT splice_region_variant, intron_variant NP_005704.1 Q9Y5P4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CERT1ENST00000261415.12 linkuse as main transcriptc.*9+5138delT intron_variant 1 ENSP00000261415.8 Q9Y5P4-1
CERT1ENST00000405807.10 linkuse as main transcriptc.*10-8delT splice_region_variant, intron_variant 5 ENSP00000383996.4 Q9Y5P4-3
CERT1ENST00000644072.2 linkuse as main transcriptc.*10-8delT splice_region_variant, intron_variant ENSP00000494110.2 Q9Y5P4-1

Frequencies

GnomAD3 genomes
AF:
0.0390
AC:
3296
AN:
84592
Hom.:
73
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.102
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0171
Gnomad ASJ
AF:
0.0258
Gnomad EAS
AF:
0.0820
Gnomad SAS
AF:
0.0553
Gnomad FIN
AF:
0.000539
Gnomad MID
AF:
0.0515
Gnomad NFE
AF:
0.00430
Gnomad OTH
AF:
0.0310
GnomAD4 exome
AF:
0.215
AC:
45013
AN:
209050
Hom.:
1
Cov.:
0
AF XY:
0.214
AC XY:
22739
AN XY:
106362
show subpopulations
Gnomad4 AFR exome
AF:
0.225
Gnomad4 AMR exome
AF:
0.218
Gnomad4 ASJ exome
AF:
0.219
Gnomad4 EAS exome
AF:
0.229
Gnomad4 SAS exome
AF:
0.212
Gnomad4 FIN exome
AF:
0.217
Gnomad4 NFE exome
AF:
0.212
Gnomad4 OTH exome
AF:
0.216
GnomAD4 genome
AF:
0.0390
AC:
3296
AN:
84612
Hom.:
74
Cov.:
29
AF XY:
0.0405
AC XY:
1622
AN XY:
40008
show subpopulations
Gnomad4 AFR
AF:
0.102
Gnomad4 AMR
AF:
0.0171
Gnomad4 ASJ
AF:
0.0258
Gnomad4 EAS
AF:
0.0826
Gnomad4 SAS
AF:
0.0549
Gnomad4 FIN
AF:
0.000539
Gnomad4 NFE
AF:
0.00430
Gnomad4 OTH
AF:
0.0317

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, no assertion criteria providedclinical testingClinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center-- -
not provided Benign:1
Likely benign, no assertion criteria providedclinical testingLaboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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: rs749454395; hg19: chr5-74670023; API