rs11601325

Variant names:

• chr11-67459535-G-A
• rs11601325
• NM_145200.5:c.*876G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145200.5(CABP4):​c.*876G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 152,168 control chromosomes in the GnomAD database, including 9,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (9090 hom., cov: 33)
  • Exomes 𝑓: 0.44 (5 hom.)
• Consequence: CABP4 NM_145200.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.454
• Publications: 15 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-67459535-G-A is Benign according to our data. Variant chr11-67459535-G-A is described in ClinVar as Benign. ClinVar VariationId is 305671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP4	NM_145200.5	c.*876G>A		3_prime_UTR_variant	Exon 6 of 6	ENST00000325656.7	NP_660201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP4	ENST00000325656.7	c.*876G>A		3_prime_UTR_variant	Exon 6 of 6	1	NM_145200.5	ENSP00000324960.5

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50405 AN: 152014 Hom.: 9092 Cov.: 33

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.444 AC: 16 AN: 36 Hom.: 5 Cov.: 0 AF XY: 0.318 AC XY: 7 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.471 AC: 16 AN: 34

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.331 AC: 50407 AN: 152132 Hom.: 9090 Cov.: 33 AF XY: 0.323 AC XY: 24025 AN XY: 74354

African (AFR) AF: 0.215 AC: 8922 AN: 41506

American (AMR) AF: 0.415 AC: 6338 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 991 AN: 3472

East Asian (EAS) AF: 0.168 AC: 869 AN: 5170

South Asian (SAS) AF: 0.219 AC: 1059 AN: 4832

European-Finnish (FIN) AF: 0.304 AC: 3215 AN: 10572

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.411 AC: 27912 AN: 67982

Other (OTH) AF: 0.326 AC: 687 AN: 2108

Alfa AF: 0.384 Hom.: 51698

Bravo AF: 0.341

Asia WGS AF: 0.234 AC: 817 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cone-rod synaptic disorder, congenital nonprogressive Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.5
DANN	Benign	0.47
PhyloP100		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11601325; hg19: chr11-67227006;