5-75374136-CTTTT-CTTT

Variant names:

• chr5-75374136-CT-C
• rs545323650
• ENST00000261415.12:c.*9+5200delA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PVS1_Moderate BS2

The NM_001379004.1(CERT1):​c.1724delA​(p.Lys575SerfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000928 in 344,644 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000079 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00010 (0 hom.)
• Consequence: CERT1 NM_001379004.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.786

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 Likely_benign. Variant got -2 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0517 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• BS2: High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001379004.1	c.1724delA	p.Lys575SerfsTer2	frameshift_variant	Exon 16 of 16		NP_001365933.1
CERT1	XM_011543090.4	c.1802delA	p.Lys601SerfsTer2	frameshift_variant	Exon 17 of 17		XP_011541392.1
CERT1	NM_001130105.1	c.*64delA		3_prime_UTR_variant	Exon 19 of 19		NP_001123577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000261415.12	c.*9+5200delA		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000642556.1	c.1724delA	p.Lys575SerfsTer2	frameshift_variant	Exon 16 of 16			ENSP00000496016.1
CERT1	ENST00000644072	c.*64delA		3_prime_UTR_variant	Exon 18 of 18			ENSP00000494110.2

Frequencies

GnomAD3 genomes AF: 0.0000867 AC: 12 AN: 138474 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000757

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000210

Gnomad SAS AF: 0.000227

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000465

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000102 AC: 21 AN: 206132 Hom.: 0 Cov.: 0 AF XY: 0.0000954 AC XY: 10 AN XY: 104798

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000160

Gnomad4 ASJ exome AF: 0.000131

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000362

Gnomad4 FIN exome AF: 0.000114

Gnomad4 NFE exome AF: 0.000106

Gnomad4 OTH exome AF: 0.000147

GnomAD4 genome AF: 0.0000794 AC: 11 AN: 138512 Hom.: 0 Cov.: 31 AF XY: 0.000120 AC XY: 8 AN XY: 66654

Gnomad4 AFR AF: 0.000160

Gnomad4 AMR AF: 0.0000756

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000211

Gnomad4 SAS AF: 0.000228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000310

Gnomad4 OTH AF: 0.00

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: rs545323650; hg19: chr5-74669961;