5-75374198-G-A

Variant names:

• chr5-75374198-G-A
• rs1233679911
• ENST00000261415.12:c.*9+5139C>T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001130105.1(CERT1):​c.*10-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (0 hom., cov: 21)
  • Exomes 𝑓: 0.00025 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CERT1 NM_001130105.1 splice_region, intron
• Scores: Splicing: ADA: 0.00002348
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0220

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-75374198-G-A is Benign according to our data. Variant chr5-75374198-G-A is described in ClinVar as [Benign]. Clinvar id is 1675987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAdExome4 at 56 AD gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00 AC: 514 AN: 83856 Hom.: 0 Cov.: 21 FAILED QC

Gnomad AFR AF: 0.00485

Gnomad AMI AF: 0.0159

Gnomad AMR AF: 0.00430

Gnomad ASJ AF: 0.00523

Gnomad EAS AF: 0.00425

Gnomad SAS AF: 0.00492

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00714

Gnomad OTH AF: 0.00275

GnomAD4 exome AF: 0.000255 AC: 56 AN: 219790 Hom.: 0 Cov.: 0 AF XY: 0.000214 AC XY: 24 AN XY: 111924

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000150

Gnomad4 ASJ exome AF: 0.000362

Gnomad4 EAS exome AF: 0.000145

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000232

Gnomad4 NFE exome AF: 0.000288

Gnomad4 OTH exome AF: 0.000275

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00613 AC: 514 AN: 83876 Hom.: 0 Cov.: 21 AF XY: 0.00627 AC XY: 249 AN XY: 39688

Gnomad4 AFR AF: 0.00484

Gnomad4 AMR AF: 0.00430

Gnomad4 ASJ AF: 0.00523

Gnomad4 EAS AF: 0.00426

Gnomad4 SAS AF: 0.00495

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.00714

Gnomad4 OTH AF: 0.00273

Alfa AF: 0.00118 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CERT1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.040		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: rs1233679911; hg19: chr5-74670023;