chr11-67454383-T-C

Variant names:

• chr11-67454383-T-C
• rs1790761
• ENST00000438189.6:c.-112-1326T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_024448615.2(CABP4):​c.-1041T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,000 control chromosomes in the GnomAD database, including 23,285 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (23285 hom., cov: 33)
• Consequence: CABP4 XM_024448615.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000438189.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP4	NM_001300896.3		c.-112-1326T>C		intron	N/A	NP_001287825.1
	CABP4	NM_001379183.1		c.-387-1051T>C		intron	N/A	NP_001366112.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP4	ENST00000438189.6	TSL:1	c.-112-1326T>C		intron	N/A	ENSP00000401555.2
	CABP4	ENST00000538060.1	TSL:4	n.296-1051T>C		intron	N/A
	CABP4	ENST00000542025.2	TSL:5	n.408-1051T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79391 AN: 151882 Hom.: 23248 Cov.: 33

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.472

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.523 AC: 79475 AN: 152000 Hom.: 23285 Cov.: 33 AF XY: 0.512 AC XY: 38009 AN XY: 74290

African (AFR) AF: 0.808 AC: 33509 AN: 41454

American (AMR) AF: 0.503 AC: 7694 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1122 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1525 AN: 5154

South Asian (SAS) AF: 0.258 AC: 1244 AN: 4826

European-Finnish (FIN) AF: 0.371 AC: 3927 AN: 10592

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29031 AN: 67904

Other (OTH) AF: 0.469 AC: 989 AN: 2110

Alfa AF: 0.479 Hom.: 2381

Bravo AF: 0.551

Asia WGS AF: 0.350 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.9
DANN	Benign	0.38
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1790761; hg19: chr11-67221854; COSMIC: COSV56888060; COSMIC: COSV56888060;