Genetic Variant CERT1:c.*9+5158G>A (chr5-75374179-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001379004.1(CERT1):c.1682G>A(p.Arg561Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000627 in 398,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

CERT1
NM_001379004.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.06

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17406648).

BP6

Variant 5-75374179-C-T is Benign according to our data. Variant chr5-75374179-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3389224.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379004.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CERT1	NM_001379004.1	c.1682G>A	p.Arg561Lys	missense	Exon 16 of 16	NP_001365933.1	A0A2R8Y7C5
CERT1	NM_001130105.1	c.*22G>A		3_prime_UTR	Exon 19 of 19	NP_001123577.1	Q9Y5P4-3
CERT1	NM_005713.3	c.*22G>A		3_prime_UTR	Exon 18 of 18	NP_005704.1	Q9Y5P4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CERT1	ENST00000261415.12	TSL:1	c.*9+5158G>A		intron	N/A	ENSP00000261415.8	Q9Y5P4-1
CERT1	ENST00000642556.1		c.1682G>A	p.Arg561Lys	missense	Exon 16 of 16	ENSP00000496016.1	A0A2R8Y7C5
CERT1	ENST00000405807.10	TSL:5	c.*22G>A		3_prime_UTR	Exon 19 of 19	ENSP00000383996.4	Q9Y5P4-3

Frequencies

GnomAD3 genomes

AF:

0.0000890

AC:

AN:

145996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000198

Gnomad SAS

AF:

0.00215

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000475

AC:

AN:

252480

Hom.:

Cov.:

AF XY:

0.0000546

AC XY:

AN XY:

128250

show subpopulations

African (AFR)

AF:

0.000278

AC:

AN:

7192

American (AMR)

AF:

0.00

AC:

AN:

7820

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9262

East Asian (EAS)

AF:

0.00

AC:

AN:

22938

South Asian (SAS)

AF:

0.00252

AC:

AN:

3574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1328

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

162694

Other (OTH)

AF:

0.0000599

AC:

AN:

16702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.0000890

AC:

AN:

146030

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

70802

show subpopulations

African (AFR)

AF:

0.0000507

AC:

AN:

39446

American (AMR)

AF:

0.00

AC:

AN:

14610

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.000199

AC:

AN:

5026

South Asian (SAS)

AF:

0.00217

AC:

AN:

4618

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67016

Other (OTH)

AF:

0.00

AC:

AN:

2036

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

(source)

DANN

Benign

0.81

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.15

MetaRNN

Benign

0.17

PhyloP100

4.1

GERP RS

5.1

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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