5-75374198-GAAAAAA-GAA

Variant names:

• chr5-75374198-GAAAA-G
• rs749454395
• ENST00000261415.12:c.*9+5135_*9+5138delTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001130105.1(CERT1):​c.*10-11_*10-8delTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 296,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000012 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0091 (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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 1933 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001130105.1	c.*10-11_*10-8delTTTT		splice_region_variant, intron_variant	Intron 18 of 18		NP_001123577.1
CERT1	NM_001379002.1	c.*9+5135_*9+5138delTTTT		intron_variant	Intron 17 of 17		NP_001365931.1
CERT1	NM_005713.3	c.*10-11_*10-8delTTTT		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+5135_*9+5138delTTTT		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000405807.10	c.*10-11_*10-8delTTTT		splice_region_variant, intron_variant	Intron 18 of 18	5		ENSP00000383996.4
CERT1	ENST00000644072.2	c.*10-11_*10-8delTTTT		splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000494110.2

Frequencies

GnomAD3 genomes AF: 0.0000118 AC: 1 AN: 84602 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000253

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00911 AC: 1933 AN: 212160 Hom.: 0 AF XY: 0.00887 AC XY: 957 AN XY: 107944

Gnomad4 AFR exome AF: 0.0101

Gnomad4 AMR exome AF: 0.00968

Gnomad4 ASJ exome AF: 0.00851

Gnomad4 EAS exome AF: 0.00858

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00958

Gnomad4 NFE exome AF: 0.00888

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0000118 AC: 1 AN: 84602 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 39976

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000253

Gnomad4 OTH AF: 0.00

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;