rs10055011

Variant names:

• chr5-75502331-G-A
• rs10055011
• NM_001379029.1:c.231+3651C>T

Variant summary

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

The NM_001379029.1(CERT1):​c.231+3651C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,084 control chromosomes in the GnomAD database, including 1,300 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 0.12 (1300 hom., cov: 32)
• Consequence: CERT1 NM_001379029.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001379029.1	c.231+3651C>T		intron_variant	Intron 2 of 16	ENST00000643780.2	NP_001365958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000643780.2	c.231+3651C>T		intron_variant	Intron 2 of 16		NM_001379029.1	ENSP00000495760.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18947 AN: 151966 Hom.: 1300 Cov.: 32

Gnomad AFR AF: 0.0969

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.125 AC: 18949 AN: 152084 Hom.: 1300 Cov.: 32 AF XY: 0.128 AC XY: 9523 AN XY: 74340

African (AFR) AF: 0.0968 AC: 4018 AN: 41506

American (AMR) AF: 0.104 AC: 1591 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 384 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1167 AN: 5180

South Asian (SAS) AF: 0.225 AC: 1081 AN: 4814

European-Finnish (FIN) AF: 0.165 AC: 1746 AN: 10562

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

European-Non Finnish (NFE) AF: 0.125 AC: 8465 AN: 67948

Other (OTH) AF: 0.113 AC: 238 AN: 2110

Alfa AF: 0.123 Hom.: 1696

Bravo AF: 0.117

Asia WGS AF: 0.195 AC: 678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.78
PhyloP100		-0.71
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: rs10055011; hg19: chr5-74798156;