5-75502331-G-A

Position:

• chr5-75502331-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379029.1(CERT1):​c.231+3651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,084 control chromosomes in the GnomAD database, including 1,300 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 0.12 (1300 hom., cov: 32)
• Consequence: CERT1 NM_001379029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERT1	NM_001379029.1	c.231+3651C>T		intron_variant		ENST00000643780.2	NP_001365958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000643780.2	c.231+3651C>T		intron_variant			NM_001379029.1	ENSP00000495760	P3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18947 AN: 151966 Hom.: 1300 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.125 AC: 18949 AN: 152084 Hom.: 1300 Cov.: 32 AF XY: 0.128 AC XY: 9523 AN XY: 74340

Gnomad4 AFR AF: 0.0968

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.113

Alfa AF: 0.124 Hom.: 1508

Bravo AF: 0.117

Asia WGS AF: 0.195 AC: 678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.78

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

LitVar

Other links and lift over

dbSNP: rs10055011; hg19: chr5-74798156;