rs16872523

Variant names:

• chr5-75369851-T-C
• rs16872523
• ENST00000261415.12:c.*10-1193A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

CERT1 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 34

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CERT1	XR_007058566.1	n.6510A>G		non_coding_transcript_exon_variant	Exon 17 of 18
CERT1	NM_005713.3	c.*4350A>G		3_prime_UTR_variant	Exon 18 of 18		NP_005704.1
CERT1	NM_031361.3	c.*4350A>G		3_prime_UTR_variant	Exon 17 of 17		NP_112729.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000261415.12	c.*10-1193A>G		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000644072.2	c.*4350A>G		3_prime_UTR_variant	Exon 18 of 18			ENSP00000494110.2
CERT1	ENST00000644445.1	c.*10-1193A>G		intron_variant	Intron 16 of 16			ENSP00000496243.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 1 AN: 12

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.326 AC: 13529 AN: 41526

American (AMR) AF: 0.0599 AC: 916 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4826

European-Finnish (FIN) AF: 0.0127 AC: 135 AN: 10624

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1791 AN: 68032

Other (OTH) AF: 0.0979 AC: 207 AN: 2114

Alfa AF: 0.0800 Hom.: 572

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
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs16872523; hg19: chr5-74665676;