rs698912

chr5-75385948-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001379029.1(CERT1):c.1371A>G(p.Glu457=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.228 in 1,586,116 control chromosomes in the GnomAD database, including 43,931 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4357 hom., cov: 32)
  • Exomes 𝑓: 0.23 (39574 hom.)
• Consequence: CERT1 NM_001379029.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.497

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 5-75385948-T-C is Benign according to our data. Variant chr5-75385948-T-C is described in ClinVar as [Benign]. Clinvar id is 1275144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.497 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CERT1	NM_001379029.1	c.1371A>G	p.Glu457=	synonymous_variant	13/17	ENST00000643780.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CERT1	ENST00000643780.2	c.1371A>G	p.Glu457=	synonymous_variant	13/17		NM_001379029.1	P3

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35691 AN: 152068 Hom.: 4351 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.227

GnomAD3 exomes AF: 0.240 AC: 56716 AN: 236308 Hom.: 7684 AF XY: 0.250 AC XY: 31995 AN XY: 127988

Gnomad AFR exome AF: 0.253

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.277

Gnomad EAS exome AF: 0.317

Gnomad SAS exome AF: 0.416

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.229

GnomAD4 exome AF: 0.227 AC: 325513 AN: 1433930 Hom.: 39574 Cov.: 31 AF XY: 0.233 AC XY: 165722 AN XY: 712372

Gnomad4 AFR exome AF: 0.263

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.337

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.235 AC: 35724 AN: 152186 Hom.: 4357 Cov.: 32 AF XY: 0.240 AC XY: 17858 AN XY: 74394

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.431

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.224

Alfa AF: 0.219 Hom.: 7103

Bravo AF: 0.227

Asia WGS AF: 0.356 AC: 1237 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CERT1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 08, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	6.6
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs698912; hg19: chr5-74681773; COSMIC: COSV54656722; COSMIC: COSV54656722;