rs1554998040

Variant names:

• chr11-67458612-CTGCCCTTCTCTCCCGCAGAGTTTGTGATGATGCTCTCCCGCCACTGAGGCTCCAGGAGGGAATATCTGTTGCCCCTGCGGCCCCAGACACCAGCCAGACCCAGGCTGCAGGCCTCCCCCAGGAGCCTCCAGGATGGAGATGGAGACCCAGCAGCCCCCAGACTACTTCTATCCCTGAAAACACCTGGCCTCAATGTTGGCTTGTTATGTTACCTGCCCACCCTCATCCTTACCTCCTCCTACTCAAGCTGCCTGGAGAAGACCTGCTCTCAGCTGCCCACCGTTCCTCAGTGTGAGCAAGATTTGGGTCTCTCCAGACCTCTGGGAGGTAGGGAGTTCCCTGGCACTGGCAGCATTCAGTGGGGACCCCCCAGTGGCATGATGAATGGAGAGGATGGCTGGACCCCTTCCACTACTTATGTTTATAATTTTTTTTTTTTTTAATGAACTTGAGCCGGGTGCAGTGGCTCACACCTGTAAGCCCAGCTGTCAGGGGGCAGAAGCGGGAGGATAGCTTGAGCCCAGGAGTGCAAGACCTGCCTGGGCAATATACTGAGACCCCATTCTCCACAAAAAGGAAAAATAAAAGACAAAAAAACAAACAAAAAACCAAAAAACCCAAGTGTAAAAAAAGTGAGCTTGAAAGAAAGAAAGGGATGGCTCCATGTATCAAAGACAAAGAAATCAAAGCTGGGGTTGTAAGAGGGAGCTGACGCTGTGGGGGTTTCAGATCTGGATGGAGGCTTGGCCGCCTGGACTCCTACAACCATGAGTGACAGAAGAACCATATGAGTCTGGGGAGCAAGAAACAAACCCCCCGGATATATTCCAGGGTCTCCAAAG-C
• rs1554998040
• NM_145200.5:c.800-18_*795del

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PVS1_Moderate PP5

The ENST00000438189.6(CABP4):​c.485-18_*795del variant causes a exon loss, splice acceptor, 3 prime UTR truncation, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CABP4 ENST00000438189.6 exon_loss, splice_acceptor, 3_prime_UTR_truncation, splice_region, intron
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.672
• Publications: 0 publications found

Genes affected

CABP4 (HGNC:1386): (calcium binding protein 4) This gene encodes a member of the CABP family of calcium binding protein characterized by four EF-hand motifs. Mutations in this gene are associated with congenital stationary night blindness type 2B. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

CABP4 Gene-Disease associations (from GenCC):

• cone-rod synaptic disorder, congenital nonprogressive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant nocturnal frontal lobe epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital stationary night blindness

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene. No cryptic splice site detected. Exon removal results in frameshift change.
• PP5: Variant 11-67458612-CTGCCCTTCTCTCCCGCAGAGTTTGTGATGATGCTCTCCCGCCACTGAGGCTCCAGGAGGGAATATCTGTTGCCCCTGCGGCCCCAGACACCAGCCAGACCCAGGCTGCAGGCCTCCCCCAGGAGCCTCCAGGATGGAGATGGAGACCCAGCAGCCCCCAGACTACTTCTATCCCTGAAAACACCTGGCCTCAATGTTGGCTTGTTATGTTACCTGCCCACCCTCATCCTTACCTCCTCCTACTCAAGCTGCCTGGAGAAGACCTGCTCTCAGCTGCCCACCGTTCCTCAGTGTGAGCAAGATTTGGGTCTCTCCAGACCTCTGGGAGGTAGGGAGTTCCCTGGCACTGGCAGCATTCAGTGGGGACCCCCCAGTGGCATGATGAATGGAGAGGATGGCTGGACCCCTTCCACTACTTATGTTTATAATTTTTTTTTTTTTTAATGAACTTGAGCCGGGTGCAGTGGCTCACACCTGTAAGCCCAGCTGTCAGGGGGCAGAAGCGGGAGGATAGCTTGAGCCCAGGAGTGCAAGACCTGCCTGGGCAATATACTGAGACCCCATTCTCCACAAAAAGGAAAAATAAAAGACAAAAAAACAAACAAAAAACCAAAAAACCCAAGTGTAAAAAAAGTGAGCTTGAAAGAAAGAAAGGGATGGCTCCATGTATCAAAGACAAAGAAATCAAAGCTGGGGTTGTAAGAGGGAGCTGACGCTGTGGGGGTTTCAGATCTGGATGGAGGCTTGGCCGCCTGGACTCCTACAACCATGAGTGACAGAAGAACCATATGAGTCTGGGGAGCAAGAAACAAACCCCCCGGATATATTCCAGGGTCTCCAAAG-C is Pathogenic according to our data. Variant chr11-67458612-CTGCCCTTCTCTCCCGCAGAGTTTGTGATGATGCTCTCCCGCCACTGAGGCTCCAGGAGGGAATATCTGTTGCCCCTGCGGCCCCAGACACCAGCCAGACCCAGGCTGCAGGCCTCCCCCAGGAGCCTCCAGGATGGAGATGGAGACCCAGCAGCCCCCAGACTACTTCTATCCCTGAAAACACCTGGCCTCAATGTTGGCTTGTTATGTTACCTGCCCACCCTCATCCTTACCTCCTCCTACTCAAGCTGCCTGGAGAAGACCTGCTCTCAGCTGCCCACCGTTCCTCAGTGTGAGCAAGATTTGGGTCTCTCCAGACCTCTGGGAGGTAGGGAGTTCCCTGGCACTGGCAGCATTCAGTGGGGACCCCCCAGTGGCATGATGAATGGAGAGGATGGCTGGACCCCTTCCACTACTTATGTTTATAATTTTTTTTTTTTTTAATGAACTTGAGCCGGGTGCAGTGGCTCACACCTGTAAGCCCAGCTGTCAGGGGGCAGAAGCGGGAGGATAGCTTGAGCCCAGGAGTGCAAGACCTGCCTGGGCAATATACTGAGACCCCATTCTCCACAAAAAGGAAAAATAAAAGACAAAAAAACAAACAAAAAACCAAAAAACCCAAGTGTAAAAAAAGTGAGCTTGAAAGAAAGAAAGGGATGGCTCCATGTATCAAAGACAAAGAAATCAAAGCTGGGGTTGTAAGAGGGAGCTGACGCTGTGGGGGTTTCAGATCTGGATGGAGGCTTGGCCGCCTGGACTCCTACAACCATGAGTGACAGAAGAACCATATGAGTCTGGGGAGCAAGAAACAAACCCCCCGGATATATTCCAGGGTCTCCAAAG-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 438232.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000438189.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP4	NM_145200.5	MANE Select	c.800-18_*795del	p.Glu267fs	frameshift stop_lost splice_region	Exon 6 of 6	NP_660201.1	P57796-1
	CABP4	NM_145200.5	MANE Select	c.800-18_*795del		splice_acceptor splice_region 3_prime_UTR intron	Exon 6 of 6	NP_660201.1	P57796-1
	CABP4	NM_001300895.3		c.485-18_*795del	p.Glu162fs	frameshift stop_lost splice_region	Exon 6 of 6	NP_001287824.1	P57796-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP4	ENST00000325656.7	TSL:1 MANE Select	c.800-18_*795del	p.Glu267fs	frameshift stop_lost splice_region	Exon 6 of 6	ENSP00000324960.5	P57796-1
	CABP4	ENST00000325656.7	TSL:1 MANE Select	c.800-18_*795del		splice_acceptor splice_region 3_prime_UTR intron	Exon 6 of 6	ENSP00000324960.5	P57796-1
	CABP4	ENST00000438189.6	TSL:1	c.485-18_*795del		exon_loss splice_acceptor 3_prime_UTR_truncation splice_region intron	Exon 7 of 7	ENSP00000401555.2	P57796-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1554998040; hg19: chr11-67226083;