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. PM4 PP5

The NM_145200.5(CABP4):​c.800-18_*795del​(p.Glu267fs) variant causes a frameshift, stop lost, splice region 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 NM_145200.5 frameshift, stop_lost, splice_region
• 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: G2P, Labcorp Genetics (formerly Invitae)
• 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.

• PM4: Stoplost variant in NM_145200.5
• 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 id is 438232.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP4	NM_145200.5	c.800-18_*795del	p.Glu267fs	frameshift_variant, stop_lost, splice_region_variant	Exon 6 of 6	ENST00000325656.7	NP_660201.1
CABP4	NM_145200.5	c.800-18_*795del		splice_acceptor_variant, splice_region_variant, 3_prime_UTR_variant, intron_variant	Exon 6 of 6	ENST00000325656.7	NP_660201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP4	ENST00000325656.7	c.800-18_*795del	p.Glu267fs	frameshift_variant, stop_lost, splice_region_variant	Exon 6 of 6	1	NM_145200.5	ENSP00000324960.5
CABP4	ENST00000325656.7	c.800-18_*795del		splice_acceptor_variant, splice_region_variant, 3_prime_UTR_variant, intron_variant	Exon 6 of 6	1	NM_145200.5	ENSP00000324960.5
CABP4	ENST00000438189.6	c.485-18_*795del		exon_loss_variant, splice_acceptor_variant, 3_prime_UTR_truncation, splice_region_variant, intron_variant	Exon 7 of 7	1		ENSP00000401555.2
CABP4	ENST00000438189.6	c.485-18_*795del		downstream_gene_variant		1		ENSP00000401555.2

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

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Retinal dystrophy Pathogenic:1

-

NIHR Bioresource Rare Diseases, University of Cambridge

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

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;