11-67458626-C-T

Variant names:

• chr11-67458626-C-T
• rs72934713
• NM_145200.5:c.800-5C>T

Variant summary

Our verdict is Benign. The variant received -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, 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, intron
• Scores: Splicing: ADA: 0.00002486
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.18
• Publications: 5 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: Benign. The variant received -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.
• 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 rank	MANE	Protein	UniProt
CABP4	NM_145200.5	c.800-5C>T		splice_region_variant, intron_variant	Intron 5 of 5	ENST00000325656.7	NP_660201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP4	ENST00000325656.7	c.800-5C>T		splice_region_variant, intron_variant	Intron 5 of 5	1	NM_145200.5	ENSP00000324960.5
CABP4	ENST00000438189.6	c.485-5C>T		splice_region_variant, intron_variant	Intron 6 of 6	1		ENSP00000401555.2

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

GnomAD2 exomes AF: 0.0589 AC: 14811 AN: 251300 AF XY: 0.0614

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 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

African (AFR) AF: 0.0141 AC: 472 AN: 33480

American (AMR) AF: 0.0291 AC: 1301 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 1625 AN: 26136

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.0541 AC: 4663 AN: 86258

European-Finnish (FIN) AF: 0.0498 AC: 2654 AN: 53340

Middle Eastern (MID) AF: 0.0923 AC: 532 AN: 5766

European-Non Finnish (NFE) AF: 0.0917 AC: 101985 AN: 1111952

Other (OTH) AF: 0.0725 AC: 4381 AN: 60394

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

African (AFR) AF: 0.0173 AC: 718 AN: 41560

American (AMR) AF: 0.0396 AC: 606 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0688 AC: 239 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0533 AC: 257 AN: 4822

European-Finnish (FIN) AF: 0.0398 AC: 422 AN: 10600

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0894 AC: 6075 AN: 67982

Other (OTH) AF: 0.0559 AC: 118 AN: 2112

Alfa AF: 0.0569 Hom.: 260

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cone-rod synaptic disorder, congenital nonprogressive Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.10
DANN	Benign	0.56
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72934713; hg19: chr11-67226097; COSMIC: COSV107351124; COSMIC: COSV107351124;