NM_145200.5:c.541+7_541+8delCAinsGC

Variant names:

• chr11-67456449-CA-GC
• rs34039523
• NM_145200.5:c.541+7_541+8delCAinsGC

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_145200.5(CABP4):​c.541+7_541+8delCAinsGC variant causes a 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CABP4 NM_145200.5 splice_region, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:2
• Conservation: PhyloP100: -0.829
• Publications: 2 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: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 11-67456449-CA-GC is Benign according to our data. Variant chr11-67456449-CA-GC is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 262579. Variant chr11-67456449-CA-GC is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 262579. Variant chr11-67456449-CA-GC is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 262579. Variant chr11-67456449-CA-GC is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 262579. Variant chr11-67456449-CA-GC is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 262579. Variant chr11-67456449-CA-GC is described in CliVar as Conflicting_classifications_of_pathogenicity. Clinvar id is 262579.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP4	NM_145200.5	c.541+7_541+8delCAinsGC		splice_region_variant, intron_variant	Intron 3 of 5	ENST00000325656.7	NP_660201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP4	ENST00000325656.7	c.541+7_541+8delCAinsGC		splice_region_variant, intron_variant	Intron 3 of 5	1	NM_145200.5	ENSP00000324960.5
CABP4	ENST00000438189.6	c.226+7_226+8delCAinsGC		splice_region_variant, intron_variant	Intron 4 of 6	1		ENSP00000401555.2
CABP4	ENST00000545777.1	n.*197+32_*197+33delCAinsGC		intron_variant	Intron 3 of 3	3		ENSP00000439145.1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Congenital Stationary Night Blindness, Recessive Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal dystrophy Uncertain:1

Jan 01, 2023

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs34039523; hg19: chr11-67223920;