11-67456449-C-G

Position:

• chr11-67456449-C-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_145200.5(CABP4):​c.541+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,607,640 control chromosomes in the GnomAD database, including 162,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (23141 hom., cov: 31)
  • Exomes 𝑓: 0.43 (139181 hom.)
• Consequence: CABP4 NM_145200.5 splice_region, intron
• Scores: Splicing: ADA: 0.00003295
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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 Benign. Variant got -16 ACMG points.

• BP6: Variant 11-67456449-C-G is Benign according to our data. Variant chr11-67456449-C-G is described in ClinVar as [Benign]. Clinvar id is 305654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79119 AN: 151440 Hom.: 23104 Cov.: 31

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.362

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.473

GnomAD3 exomes AF: 0.430 AC: 105195 AN: 244800 Hom.: 24720 AF XY: 0.411 AC XY: 54634 AN XY: 132960

Gnomad AFR exome AF: 0.814

Gnomad AMR exome AF: 0.579

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.284

Gnomad SAS exome AF: 0.268

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.415

GnomAD4 exome AF: 0.429 AC: 624514 AN: 1456082 Hom.: 139181 Cov.: 60 AF XY: 0.421 AC XY: 304964 AN XY: 724324

Gnomad4 AFR exome AF: 0.820

Gnomad4 AMR exome AF: 0.575

Gnomad4 ASJ exome AF: 0.319

Gnomad4 EAS exome AF: 0.307

Gnomad4 SAS exome AF: 0.274

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.428

GnomAD4 genome AF: 0.523 AC: 79202 AN: 151558 Hom.: 23141 Cov.: 31 AF XY: 0.511 AC XY: 37854 AN XY: 74018

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.503

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.427

Gnomad4 OTH AF: 0.470

Alfa AF: 0.448 Hom.: 3806

Bravo AF: 0.551

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 05, 2018	This variant is associated with the following publications: (PMID: 27259154) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 21, 2023	- -

Cone-rod synaptic disorder, congenital nonprogressive Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000033
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		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; COSMIC: COSV56886598; COSMIC: COSV56886598;