chr5-75491485-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001379029.1(CERT1):​c.231+14497A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379029.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERT1	NM_001379029.1	MANE Select	c.231+14497A>T		intron	N/A	NP_001365958.1	Q9Y5P4-1
	CERT1	NM_001130105.1		c.615+14497A>T		intron	N/A	NP_001123577.1	Q9Y5P4-3
	CERT1	NM_001379002.1		c.231+14497A>T		intron	N/A	NP_001365931.1	Q9Y5P4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERT1	ENST00000643780.2	MANE Select	c.231+14497A>T		intron	N/A	ENSP00000495760.1	Q9Y5P4-1
	CERT1	ENST00000261415.12	TSL:1	c.231+14497A>T		intron	N/A	ENSP00000261415.8	Q9Y5P4-1
	CERT1	ENST00000405807.10	TSL:5	c.615+14497A>T		intron	N/A	ENSP00000383996.4	Q9Y5P4-3

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.67
PhyloP100		-0.058

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;