rs16872523

Positions:

• chr5-75369851-T-C

Variant summary

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

The ENST00000261415.12(CERT1):​c.*10-1193A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,306 control chromosomes in the GnomAD database, including 2,339 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 0.11 (2339 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: CERT1 ENST00000261415.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERT1	NM_005713.3	c.*4350A>G		3_prime_UTR_variant	18/18
CERT1	NM_031361.3	c.*4350A>G		3_prime_UTR_variant	17/17
CERT1	XM_011543090.4	c.*4192A>G		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERT1	ENST00000261415.12	c.*10-1193A>G		intron_variant		1		P3
CERT1	ENST00000644072.2	c.*4350A>G		3_prime_UTR_variant	18/18			P3
CERT1	ENST00000642809.1	c.*10-1193A>G		intron_variant				A1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16711 AN: 152174 Hom.: 2334 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0599

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0127

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.0994

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0833

GnomAD4 genome AF: 0.110 AC: 16750 AN: 152292 Hom.: 2339 Cov.: 32 AF XY: 0.105 AC XY: 7800 AN XY: 74472

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.0599

Gnomad4 ASJ AF: 0.0360

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.0127

Gnomad4 NFE AF: 0.0263

Gnomad4 OTH AF: 0.0979

Alfa AF: 0.0800 Hom.: 495

Bravo AF: 0.125

Asia WGS AF: 0.0240 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16872523; hg19: chr5-74665676;