5-75374198-GAAAAAA-GAAA

Variant names:

• chr5-75374198-GAAA-G
• rs749454395
• ENST00000261415.12:c.*9+5136_*9+5138delTTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001130105.1(CERT1):​c.*10-10_*10-8delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.018 in 292,562 control chromosomes in the GnomAD database, including 1 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 0.0019 (1 hom., cov: 29)
  • Exomes 𝑓: 0.025 (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-GAAA-G is Benign according to our data. Variant chr5-75374198-GAAA-G is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00186 (157/84610) while in subpopulation EAS AF= 0.0438 (135/3084). AF 95% confidence interval is 0.0378. There are 1 homozygotes in gnomad4. There are 84 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 157 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00186 AC: 157 AN: 84590 Hom.: 1 Cov.: 29

Gnomad AFR AF: 0.000408

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0436

Gnomad SAS AF: 0.00339

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000253

Gnomad OTH AF: 0.000912

GnomAD4 exome AF: 0.0246 AC: 5110 AN: 207952 Hom.: 0 AF XY: 0.0241 AC XY: 2542 AN XY: 105692

Gnomad4 AFR exome AF: 0.0266

Gnomad4 AMR exome AF: 0.0234

Gnomad4 ASJ exome AF: 0.0231

Gnomad4 EAS exome AF: 0.0350

Gnomad4 SAS exome AF: 0.0251

Gnomad4 FIN exome AF: 0.0204

Gnomad4 NFE exome AF: 0.0233

Gnomad4 OTH exome AF: 0.0275

GnomAD4 genome AF: 0.00186 AC: 157 AN: 84610 Hom.: 1 Cov.: 29 AF XY: 0.00210 AC XY: 84 AN XY: 39996

Gnomad4 AFR AF: 0.000408

Gnomad4 AMR AF: 0.000138

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0438

Gnomad4 SAS AF: 0.00341

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000253

Gnomad4 OTH AF: 0.000906

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;