chr11-67456449-C-A

Position:

• chr11-67456449-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145200.5(CABP4):​c.541+7C>A 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. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CABP4 NM_145200.5 splice_region, intron
• Scores: Splicing: ADA: 0.000007711
• Clinical Significance: Not reported in ClinVar
• 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]

CABP4 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABP4	NM_145200.5	c.541+7C>A		splice_region_variant, intron_variant		ENST00000325656.7	NP_660201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABP4	ENST00000325656.7	c.541+7C>A		splice_region_variant, intron_variant		1	NM_145200.5	ENSP00000324960.5
CABP4	ENST00000438189.6	c.226+7C>A		splice_region_variant, intron_variant		1		ENSP00000401555.2
CABP4	ENST00000545777.1	n.*197+32C>A		intron_variant		3		ENSP00000439145.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456240 Hom.: 0 Cov.: 60 AF XY: 0.00 AC XY: 0 AN XY: 724422

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	16
DANN	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000077
SpliceAI score (max)		0.94		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.94		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1638564; hg19: chr11-67223920;