rs11601325

Positions:

• chr11-67459535-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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/exons	MANE	Protein	UniProt
CABP4	NM_145200.5	c.*876G>A		3_prime_UTR_variant	6/6	ENST00000325656.7	NP_660201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABP4	ENST00000325656.7	c.*876G>A		3_prime_UTR_variant	6/6	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

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.471

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

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.411

Gnomad4 OTH AF: 0.326

Alfa AF: 0.389 Hom.: 23905

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

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. -

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs11601325; hg19: chr11-67227006;