rs3827608

Variant names:

• chr5-75391764-T-C
• rs3827608
• NM_001379029.1:c.1189-2077A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-75391764-T-C
• chr5-75391764-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379029.1(CERT1):​c.1189-2077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 152,262 control chromosomes in the GnomAD database, including 562 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 0.078 (562 hom., cov: 32)
• Consequence: CERT1 NM_001379029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379029.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERT1	NM_001379029.1	MANE Select	c.1189-2077A>G		intron	N/A	NP_001365958.1	Q9Y5P4-1
	CERT1	NM_001130105.1		c.1573-2077A>G		intron	N/A	NP_001123577.1	Q9Y5P4-3
	CERT1	NM_001379002.1		c.1189-2077A>G		intron	N/A	NP_001365931.1	Q9Y5P4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERT1	ENST00000643780.2	MANE Select	c.1189-2077A>G		intron	N/A	ENSP00000495760.1	Q9Y5P4-1
	CERT1	ENST00000261415.12	TSL:1	c.1189-2077A>G		intron	N/A	ENSP00000261415.8	Q9Y5P4-1
	CERT1	ENST00000405807.10	TSL:5	c.1573-2077A>G		intron	N/A	ENSP00000383996.4	Q9Y5P4-3

Frequencies

GnomAD3 genomes AF: 0.0782 AC: 11903 AN: 152144 Hom.: 558 Cov.: 32

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0708

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0885

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0783 AC: 11919 AN: 152262 Hom.: 562 Cov.: 32 AF XY: 0.0798 AC XY: 5944 AN XY: 74444

African (AFR) AF: 0.0604 AC: 2512 AN: 41556

American (AMR) AF: 0.0682 AC: 1042 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 530 AN: 3470

East Asian (EAS) AF: 0.0706 AC: 366 AN: 5184

South Asian (SAS) AF: 0.169 AC: 814 AN: 4824

European-Finnish (FIN) AF: 0.0681 AC: 722 AN: 10608

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5695 AN: 68014

Other (OTH) AF: 0.0866 AC: 183 AN: 2112

Alfa AF: 0.0773 Hom.: 50

Bravo AF: 0.0749

Asia WGS AF: 0.117 AC: 405 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.2
DANN	Benign	0.75
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3827608; hg19: chr5-74687589;