Variant 5-75374136-C-CT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PVS1_ModerateBP6_ModerateBS2

The NM_001379004.1(CERT1):c.1724dupA(p.Leu576AlafsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00795 in 324,058 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 1 hom., cov: 31)

Exomes 𝑓: 0.011 ( 2 hom. )

Consequence

CERT1
NM_001379004.1 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.786

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]

CERT1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0517 CDS is truncated, and there are 0 pathogenic variants in the truncated region.

BP6

Variant 5-75374136-C-CT is Benign according to our data. Variant chr5-75374136-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 2673015.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 467 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
CERT1	NM_001379004.1 link	c.1724dupA	p.Leu576AlafsTer26	frameshift_variant	Exon 16 of 16	NP_001365933.1
CERT1	XM_011543090.4 link	c.1802dupA	p.Leu602AlafsTer26	frameshift_variant	Exon 17 of 17	XP_011541392.1
CERT1	NM_001130105.1 link	c.*64dupA		3_prime_UTR_variant	Exon 19 of 19	NP_001123577.1	Q9Y5P4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
CERT1	ENST00000261415.12 link	c.*9+5200dupA		intron_variant	Intron 17 of 17	1	ENSP00000261415.8	Q9Y5P4-1
CERT1	ENST00000642556.1 link	c.1724dupA	p.Leu576AlafsTer26	frameshift_variant	Exon 16 of 16		ENSP00000496016.1	A0A2R8Y7C5
CERT1	ENST00000644072 link	c.*64dupA		3_prime_UTR_variant	Exon 18 of 18		ENSP00000494110.2	Q9Y5P4-1

Frequencies

GnomAD3 genomes

AF:

0.00337

AC:

466

AN:

138444

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000696

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000984

Gnomad ASJ

AF:

0.00687

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000455

Gnomad FIN

AF:

0.00865

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00513

Gnomad OTH

AF:

0.00162

GnomAD4 exome

AF:

0.0114

AC:

2108

AN:

185576

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

1068

AN XY:

94444

show subpopulations

Gnomad4 AFR exome

AF:

0.00712

Gnomad4 AMR exome

AF:

0.00622

Gnomad4 ASJ exome

AF:

0.0106

Gnomad4 EAS exome

AF:

0.00443

Gnomad4 SAS exome

AF:

0.00681

Gnomad4 FIN exome

AF:

0.0206

Gnomad4 NFE exome

AF:

0.0120

Gnomad4 OTH exome

AF:

0.00937

GnomAD4 genome

AF:

0.00337

AC:

467

AN:

138482

Hom.:

Cov.:

AF XY:

0.00348

AC XY:

232

AN XY:

66638

show subpopulations

Gnomad4 AFR

AF:

0.000721

Gnomad4 AMR

AF:

0.000983

Gnomad4 ASJ

AF:

0.00687

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000457

Gnomad4 FIN

AF:

0.00865

Gnomad4 NFE

AF:

0.00513

Gnomad4 OTH

AF:

0.00161

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CERT1: BS1 -

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.

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