11-67458626-C-T

Position:

• chr11-67458626-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145200.5(CABP4):​c.800-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0781 in 1,613,978 control chromosomes in the GnomAD database, including 5,679 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (339 hom., cov: 32)
  • Exomes 𝑓: 0.080 (5340 hom.)
• Consequence: CABP4 NM_145200.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002486
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.18

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-67458626-C-T is Benign according to our data. Variant chr11-67458626-C-T is described in ClinVar as [Benign]. Clinvar id is 262580.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-67458626-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CABP4	NM_145200.5	c.800-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000325656.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CABP4	ENST00000325656.7	c.800-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_145200.5	P1
CABP4	ENST00000438189.6	c.485-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8513 AN: 152110 Hom.: 340 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0398

Gnomad ASJ AF: 0.0688

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0398

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0894

Gnomad OTH AF: 0.0565

GnomAD3 exomes AF: 0.0589 AC: 14811 AN: 251300 Hom.: 548 AF XY: 0.0614 AC XY: 8341 AN XY: 135862

Gnomad AFR exome AF: 0.0176

Gnomad AMR exome AF: 0.0274

Gnomad ASJ exome AF: 0.0638

Gnomad EAS exome AF: 0.000652

Gnomad SAS exome AF: 0.0540

Gnomad FIN exome AF: 0.0459

Gnomad NFE exome AF: 0.0867

Gnomad OTH exome AF: 0.0702

GnomAD4 exome AF: 0.0805 AC: 117622 AN: 1461750 Hom.: 5340 Cov.: 32 AF XY: 0.0800 AC XY: 58202 AN XY: 727172

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0291

Gnomad4 ASJ exome AF: 0.0622

Gnomad4 EAS exome AF: 0.000227

Gnomad4 SAS exome AF: 0.0541

Gnomad4 FIN exome AF: 0.0498

Gnomad4 NFE exome AF: 0.0917

Gnomad4 OTH exome AF: 0.0725

GnomAD4 genome AF: 0.0559 AC: 8504 AN: 152228 Hom.: 339 Cov.: 32 AF XY: 0.0527 AC XY: 3924 AN XY: 74420

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0688

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.0398

Gnomad4 NFE AF: 0.0894

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0645 Hom.: 191

Bravo AF: 0.0535

Asia WGS AF: 0.0230 AC: 80 AN: 3478

EpiCase AF: 0.0891

EpiControl AF: 0.0846

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	- -

Cone-rod synaptic disorder, congenital nonprogressive Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs72934713; hg19: chr11-67226097;