chr5-75374198-G-GA

Variant names:

• chr5-75374198-G-GA
• rs749454395
• ENST00000261415.12:c.*9+5138_*9+5139insT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001130105.1(CERT1):​c.*10-8dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 301,794 control chromosomes in the GnomAD database, including 3 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0050 (3 hom., cov: 29)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: CERT1 NM_001130105.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001130105.1	c.*10-8dupT		splice_region_variant, intron_variant	Intron 18 of 18		NP_001123577.1
CERT1	NM_001379002.1	c.*9+5138dupT		intron_variant	Intron 17 of 17		NP_001365931.1
CERT1	NM_005713.3	c.*10-8dupT		splice_region_variant, intron_variant	Intron 17 of 17		NP_005704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000261415.12	c.*9+5138_*9+5139insT		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000405807.10	c.*10-8_*10-7insT		splice_region_variant, intron_variant	Intron 18 of 18	5		ENSP00000383996.4
CERT1	ENST00000644072.2	c.*10-8_*10-7insT		splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000494110.2

Frequencies

GnomAD3 genomes AF: 0.00505 AC: 427 AN: 84518 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.00601

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.000468

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.00715

Gnomad FIN AF: 0.00378

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.00301

Gnomad OTH AF: 0.00456

GnomAD4 exome AF: 0.0711 AC: 15454 AN: 217256 Hom.: 0 Cov.: 0 AF XY: 0.0721 AC XY: 7979 AN XY: 110628

Gnomad4 AFR exome AF: 0.0588

Gnomad4 AMR exome AF: 0.0638

Gnomad4 ASJ exome AF: 0.0703

Gnomad4 EAS exome AF: 0.0695

Gnomad4 SAS exome AF: 0.0606

Gnomad4 FIN exome AF: 0.0811

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.0702

GnomAD4 genome AF: 0.00504 AC: 426 AN: 84538 Hom.: 3 Cov.: 29 AF XY: 0.00553 AC XY: 221 AN XY: 39970

Gnomad4 AFR AF: 0.00604

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.000468

Gnomad4 EAS AF: 0.0269

Gnomad4 SAS AF: 0.00720

Gnomad4 FIN AF: 0.00378

Gnomad4 NFE AF: 0.00301

Gnomad4 OTH AF: 0.00453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs749454395; hg19: chr5-74670023;