5-75491485-T-C

Variant names:

• chr5-75491485-T-C
• rs6896136
• NM_001379029.1:c.231+14497A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379029.1(CERT1):​c.231+14497A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,910 control chromosomes in the GnomAD database, including 25,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (25629 hom., cov: 30)
• Consequence: CERT1 NM_001379029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 12 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001379029.1	c.231+14497A>G		intron_variant	Intron 2 of 16	ENST00000643780.2	NP_001365958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000643780.2	c.231+14497A>G		intron_variant	Intron 2 of 16		NM_001379029.1	ENSP00000495760.1

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82466 AN: 151794 Hom.: 25577 Cov.: 30

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.495

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.544 AC: 82577 AN: 151910 Hom.: 25629 Cov.: 30 AF XY: 0.546 AC XY: 40497 AN XY: 74206

African (AFR) AF: 0.866 AC: 35874 AN: 41448

American (AMR) AF: 0.455 AC: 6932 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1680 AN: 3470

East Asian (EAS) AF: 0.533 AC: 2747 AN: 5154

South Asian (SAS) AF: 0.586 AC: 2822 AN: 4818

European-Finnish (FIN) AF: 0.443 AC: 4665 AN: 10536

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.388 AC: 26369 AN: 67936

Other (OTH) AF: 0.491 AC: 1036 AN: 2108

Alfa AF: 0.438 Hom.: 8184

Bravo AF: 0.553

Asia WGS AF: 0.583 AC: 2026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.60
PhyloP100		-0.058
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6896136; hg19: chr5-74787310;