rs34039523

chr11-67456449-CA-GCchr11-67456449-CA-GT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP6

The NM_145200.5(CABP4):c.541+7_541+8delinsGC 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. 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:1 B:2
• Conservation: PhyloP100: -0.829

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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 id is 262579.We mark this variant Likely_benign, oryginal submissions are: {Benign=2, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CABP4	NM_145200.5	c.541+7_541+8delinsGC		splice_region_variant, intron_variant		ENST00000325656.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CABP4	ENST00000325656.7	c.541+7_541+8delinsGC		splice_region_variant, intron_variant		1	NM_145200.5	P1
CABP4	ENST00000438189.6	c.226+7_226+8delinsGC		splice_region_variant, intron_variant		1
CABP4	ENST00000545777.1	c.*197+32_*197+33delinsGC		intron_variant, NMD_transcript_variant		3

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:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Congenital Stationary Night Blindness, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34039523; hg19: chr11-67223920;