Genetic Variant ENST00000261415.12:c.*9+5138_*9+5139insTTT (chr5-75374198-G-GAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000261415.12(CERT1):c.*9+5138_*9+5139insTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 304,394 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

CERT1
ENST00000261415.12 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.108

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 34
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

CERT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000261415.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
CERT1	NM_001130105.1	c.10-10_10-8dupTTT	splice_region intron	N/A	NP_001123577.1	Q9Y5P4-3
CERT1	NM_001379002.1	c.9+5136_9+5138dupTTT	intron	N/A	NP_001365931.1	Q9Y5P4-1
CERT1	NM_005713.3	c.10-10_10-8dupTTT	splice_region intron	N/A	NP_005704.1	Q9Y5P4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CERT1	ENST00000261415.12	TSL:1	c.9+5138_9+5139insTTT	intron	N/A	ENSP00000261415.8	Q9Y5P4-1
CERT1	ENST00000405807.10	TSL:5	c.10-8_10-7insTTT	splice_region intron	N/A	ENSP00000383996.4	Q9Y5P4-3
CERT1	ENST00000957920.1		c.10-8_10-7insTTT	splice_region intron	N/A	ENSP00000627979.1

Frequencies

GnomAD3 genomes

AF:

0.0000709

AC:

AN:

84604

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000408

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00188

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

AN:

219770

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

AN XY:

111924

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000314

AC:

AN:

6366

American (AMR)

AF:

0.000150

AC:

AN:

6666

Ashkenazi Jewish (ASJ)

AF:

0.000362

AC:

AN:

8282

East Asian (EAS)

AF:

0.0000968

AC:

AN:

20666

South Asian (SAS)

AF:

0.000806

AC:

AN:

2482

European-Finnish (FIN)

AF:

0.0000581

AC:

AN:

17204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1152

European-Non Finnish (NFE)

AF:

0.000154

AC:

AN:

142408

Other (OTH)

AF:

0.000206

AC:

AN:

14544

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.260

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000591

AC:

AN:

84624

Hom.:

Cov.:

AF XY:

0.000100

AC XY:

AN XY:

40008

show subpopulations

African (AFR)

AF:

0.0000408

AC:

AN:

24524

American (AMR)

AF:

0.00

AC:

AN:

7256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2136

East Asian (EAS)

AF:

0.00

AC:

AN:

3086

South Asian (SAS)

AF:

0.00152

AC:

AN:

2640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

128

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

39536

Other (OTH)

AF:

0.00

AC:

AN:

1104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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ENST00000261415.12:c.9+5138_9+5139insTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over