rs34039523

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-67456449-CA-GC
• chr11-67456449-CA-GT

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: Benign criteria provided, multiple submitters, no conflicts U:1 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 ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 262579.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145200.5. 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.541+7_541+8delCAinsGC		splice_region intron	N/A	NP_660201.1	P57796-1
	CABP4	NM_001300895.3		c.226+7_226+8delCAinsGC		splice_region intron	N/A	NP_001287824.1	P57796-2
	CABP4	NM_001300896.3		c.226+7_226+8delCAinsGC		splice_region intron	N/A	NP_001287825.1	P57796-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP4	ENST00000325656.7	TSL:1 MANE Select	c.541+7_541+8delCAinsGC		splice_region intron	N/A	ENSP00000324960.5	P57796-1
	CABP4	ENST00000438189.6	TSL:1	c.226+7_226+8delCAinsGC		splice_region intron	N/A	ENSP00000401555.2	P57796-2
	CABP4	ENST00000545777.1	TSL:3	n.*197+32_*197+33delCAinsGC		intron	N/A	ENSP00000439145.1	F5H3E8

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	1	-	Retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.83

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs34039523;

hg19: chr11-67223920;