11-67456449-C-G

Variant names:

• chr11-67456449-C-G
• rs1638564
• NM_145200.5:c.541+7C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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: Labcorp Genetics (formerly Invitae), G2P
• 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145200.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP4	NM_145200.5	MANE Select	c.541+7C>G		splice_region intron	N/A	NP_660201.1	P57796-1
	CABP4	NM_001300895.3		c.226+7C>G		splice_region intron	N/A	NP_001287824.1	P57796-2
	CABP4	NM_001300896.3		c.226+7C>G		splice_region intron	N/A	NP_001287825.1	P57796-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CABP4	ENST00000325656.7	TSL:1 MANE Select	c.541+7C>G		splice_region intron	N/A	ENSP00000324960.5	P57796-1
	CABP4	ENST00000438189.6	TSL:1	c.226+7C>G		splice_region intron	N/A	ENSP00000401555.2	P57796-2
	CABP4	ENST00000545777.1	TSL:3	n.*197+32C>G		intron	N/A	ENSP00000439145.1	F5H3E8

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

GnomAD2 exomes AF: 0.430 AC: 105195 AN: 244800 AF XY: 0.411

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 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

African (AFR) AF: 0.820 AC: 27455 AN: 33466

American (AMR) AF: 0.575 AC: 25566 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 8329 AN: 26116

East Asian (EAS) AF: 0.307 AC: 12191 AN: 39670

South Asian (SAS) AF: 0.274 AC: 23587 AN: 86210

European-Finnish (FIN) AF: 0.376 AC: 18224 AN: 48468

Middle Eastern (MID) AF: 0.380 AC: 2189 AN: 5760

European-Non Finnish (NFE) AF: 0.433 AC: 481165 AN: 1111588

Other (OTH) AF: 0.428 AC: 25808 AN: 60322

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

African (AFR) AF: 0.808 AC: 33367 AN: 41310

American (AMR) AF: 0.503 AC: 7670 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1119 AN: 3462

East Asian (EAS) AF: 0.293 AC: 1496 AN: 5098

South Asian (SAS) AF: 0.258 AC: 1246 AN: 4826

European-Finnish (FIN) AF: 0.374 AC: 3929 AN: 10506

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.427 AC: 28955 AN: 67798

Other (OTH) AF: 0.470 AC: 989 AN: 2104

Alfa AF: 0.448 Hom.: 3806

Bravo AF: 0.551

Asia WGS AF: 0.353 AC: 1228 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Cone-rod synaptic disorder, congenital nonprogressive (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	10
DANN	Benign	0.58
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1638564; hg19: chr11-67223920; COSMIC: COSV56886598; COSMIC: COSV56886598;