chr5-75374198-G-GAAA

Variant names:

• chr5-75374198-G-GAAA
• rs749454395
• ENST00000261415.12:c.*9+5138_*9+5139insTTT

Variant summary

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

The NM_001130105.1(CERT1):​c.*10-10_*10-8dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 304,394 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 29)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: CERT1 NM_001130105.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.108

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 GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001130105.1	c.*10-10_*10-8dupTTT		splice_region_variant, intron_variant	Intron 18 of 18		NP_001123577.1
CERT1	NM_001379002.1	c.*9+5136_*9+5138dupTTT		intron_variant	Intron 17 of 17		NP_001365931.1
CERT1	NM_005713.3	c.*10-10_*10-8dupTTT		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+5138_*9+5139insTTT		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000405807.10	c.*10-8_*10-7insTTT		splice_region_variant, intron_variant	Intron 18 of 18	5		ENSP00000383996.4
CERT1	ENST00000644072.2	c.*10-8_*10-7insTTT		splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000494110.2

Frequencies

GnomAD3 genomes AF: 0.0000709 AC: 6 AN: 84604 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00188

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000164 AC: 36 AN: 219770 Hom.: 0 Cov.: 0 AF XY: 0.000205 AC XY: 23 AN XY: 111924

Gnomad4 AFR exome AF: 0.000314

Gnomad4 AMR exome AF: 0.000150

Gnomad4 ASJ exome AF: 0.000362

Gnomad4 EAS exome AF: 0.0000968

Gnomad4 SAS exome AF: 0.000806

Gnomad4 FIN exome AF: 0.0000581

Gnomad4 NFE exome AF: 0.000154

Gnomad4 OTH exome AF: 0.000206

GnomAD4 genome AF: 0.0000591 AC: 5 AN: 84624 Hom.: 0 Cov.: 29 AF XY: 0.000100 AC XY: 4 AN XY: 40008

Gnomad4 AFR AF: 0.0000408

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00152

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;