5-75374046-T-C

Variant names:

• chr5-75374046-T-C
• rs1257682813
• ENST00000261415.12:c.*9+5291A>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001379004.1(CERT1):​c.1815A>G​(p.Gln605Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 246,510 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000081 (0 hom.)
• Consequence: CERT1 NM_001379004.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0280

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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-75374046-T-C is Benign according to our data. Variant chr5-75374046-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2655535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.028 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001379004.1	c.1815A>G	p.Gln605Gln	synonymous_variant	Exon 16 of 16		NP_001365933.1
CERT1	XM_011543090.4	c.1893A>G	p.Gln631Gln	synonymous_variant	Exon 17 of 17		XP_011541392.1
CERT1	NM_001130105.1	c.*155A>G		3_prime_UTR_variant	Exon 19 of 19		NP_001123577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000261415.12	c.*9+5291A>G		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000642556.1	c.1815A>G	p.Gln605Gln	synonymous_variant	Exon 16 of 16			ENSP00000496016.1
CERT1	ENST00000644072	c.*155A>G		3_prime_UTR_variant	Exon 18 of 18			ENSP00000494110.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000811 AC: 2 AN: 246510 Hom.: 0 Cov.: 0 AF XY: 0.00000800 AC XY: 1 AN XY: 124956

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000134

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000632

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CERT1: PM2:Supporting, BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.0
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs1257682813; hg19: chr5-74669871;