5-75510279-C-T

Variant names:

• chr5-75510279-C-T
• rs5744533
• NM_001379029.1:c.96+833G>A

Variant summary

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

The NM_001379029.1(CERT1):​c.96+833G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 151,850 control chromosomes in the GnomAD database, including 4,312 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 0.23 (4312 hom., cov: 31)
• Consequence: CERT1 NM_001379029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

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.96+833G>A		intron	N/A	NP_001365958.1	Q9Y5P4-1
	CERT1	NM_001130105.1		c.480+833G>A		intron	N/A	NP_001123577.1	Q9Y5P4-3
	CERT1	NM_001379002.1		c.96+833G>A		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.96+833G>A		intron	N/A	ENSP00000495760.1	Q9Y5P4-1
	CERT1	ENST00000261415.12	TSL:1	c.96+833G>A		intron	N/A	ENSP00000261415.8	Q9Y5P4-1
	CERT1	ENST00000405807.10	TSL:5	c.480+833G>A		intron	N/A	ENSP00000383996.4	Q9Y5P4-3

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35520 AN: 151732 Hom.: 4302 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.234 AC: 35559 AN: 151850 Hom.: 4312 Cov.: 31 AF XY: 0.240 AC XY: 17776 AN XY: 74196

African (AFR) AF: 0.256 AC: 10586 AN: 41354

American (AMR) AF: 0.182 AC: 2784 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 971 AN: 3468

East Asian (EAS) AF: 0.325 AC: 1682 AN: 5168

South Asian (SAS) AF: 0.431 AC: 2072 AN: 4806

European-Finnish (FIN) AF: 0.235 AC: 2465 AN: 10508

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14207 AN: 67956

Other (OTH) AF: 0.223 AC: 470 AN: 2112

Alfa AF: 0.160 Hom.: 461

Bravo AF: 0.226

Asia WGS AF: 0.357 AC: 1240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.28
DANN	Benign	0.74
PhyloP100		-1.4
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: rs5744533; hg19: chr5-74806104; COSMIC: COSV54039658; COSMIC: COSV54039658;