5-75374198-GAAAAAA-GAAAA

Variant names:

• chr5-75374198-GAA-G
• rs749454395
• ENST00000261415.12:c.*9+5137_*9+5138delTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001130105.1(CERT1):​c.*10-9_*10-8delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 286,150 control chromosomes in the GnomAD database, including 40 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.025 (40 hom., cov: 29)
  • Exomes 𝑓: 0.070 (0 hom.)
• Consequence: CERT1 NM_001130105.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131

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 -9 ACMG points.

• BP6: Variant 5-75374198-GAA-G is Benign according to our data. Variant chr5-75374198-GAA-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001130105.1	c.*10-9_*10-8delTT		splice_region_variant, intron_variant	Intron 18 of 18		NP_001123577.1
CERT1	NM_001379002.1	c.*9+5137_*9+5138delTT		intron_variant	Intron 17 of 17		NP_001365931.1
CERT1	NM_005713.3	c.*10-9_*10-8delTT		splice_region_variant, intron_variant	Intron 17 of 17		NP_005704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000261415.12	c.*9+5137_*9+5138delTT		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000405807.10	c.*10-9_*10-8delTT		splice_region_variant, intron_variant	Intron 18 of 18	5		ENSP00000383996.4
CERT1	ENST00000644072.2	c.*10-9_*10-8delTT		splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000494110.2

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 2133 AN: 84562 Hom.: 40 Cov.: 29

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00924

Gnomad ASJ AF: 0.000468

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00715

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0147

Gnomad NFE AF: 0.000304

Gnomad OTH AF: 0.0155

GnomAD4 exome AF: 0.0699 AC: 14080 AN: 201568 Hom.: 0 AF XY: 0.0690 AC XY: 7076 AN XY: 102528

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0687

Gnomad4 ASJ exome AF: 0.0674

Gnomad4 EAS exome AF: 0.0645

Gnomad4 SAS exome AF: 0.0713

Gnomad4 FIN exome AF: 0.0675

Gnomad4 NFE exome AF: 0.0687

Gnomad4 OTH exome AF: 0.0722

GnomAD4 genome AF: 0.0253 AC: 2136 AN: 84582 Hom.: 40 Cov.: 29 AF XY: 0.0257 AC XY: 1026 AN XY: 39984

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.00923

Gnomad4 ASJ AF: 0.000468

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00720

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000304

Gnomad4 OTH AF: 0.0154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs749454395; hg19: chr5-74670023;