rs17501521

Variant names:

• chr11-67457517-C-T
• rs17501521
• NM_145200.5:c.542-56C>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.542-56C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 1,467,236 control chromosomes in the GnomAD database, including 81,411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5719 hom., cov: 32)
  • Exomes 𝑓: 0.33 (75692 hom.)
• Consequence: CABP4 NM_145200.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.459
• Publications: 16 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 11-67457517-C-T is Benign according to our data. Variant chr11-67457517-C-T is described in ClinVar as Benign. ClinVar VariationId is 1247835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CABP4	NM_145200.5	c.542-56C>T		intron_variant	Intron 3 of 5	ENST00000325656.7	NP_660201.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CABP4	ENST00000325656.7	c.542-56C>T		intron_variant	Intron 3 of 5	1	NM_145200.5	ENSP00000324960.5
CABP4	ENST00000438189.6	c.227-56C>T		intron_variant	Intron 4 of 6	1		ENSP00000401555.2
CABP4	ENST00000545777.1	n.*198-56C>T		intron_variant	Intron 3 of 3	3		ENSP00000439145.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38766 AN: 151896 Hom.: 5722 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.0844

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.258

GnomAD4 exome AF: 0.329 AC: 433108 AN: 1315222 Hom.: 75692 AF XY: 0.326 AC XY: 212905 AN XY: 653104

African (AFR) AF: 0.133 AC: 3996 AN: 30006

American (AMR) AF: 0.176 AC: 6271 AN: 35662

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5485 AN: 24628

East Asian (EAS) AF: 0.0880 AC: 3127 AN: 35552

South Asian (SAS) AF: 0.208 AC: 16179 AN: 77682

European-Finnish (FIN) AF: 0.268 AC: 13132 AN: 49004

Middle Eastern (MID) AF: 0.296 AC: 1635 AN: 5530

European-Non Finnish (NFE) AF: 0.366 AC: 366682 AN: 1001920

Other (OTH) AF: 0.301 AC: 16601 AN: 55238

GnomAD4 genome AF: 0.255 AC: 38759 AN: 152014 Hom.: 5719 Cov.: 32 AF XY: 0.247 AC XY: 18323 AN XY: 74314

African (AFR) AF: 0.137 AC: 5698 AN: 41480

American (AMR) AF: 0.206 AC: 3147 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3466

East Asian (EAS) AF: 0.0840 AC: 435 AN: 5178

South Asian (SAS) AF: 0.192 AC: 923 AN: 4804

European-Finnish (FIN) AF: 0.264 AC: 2788 AN: 10570

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24094 AN: 67940

Other (OTH) AF: 0.256 AC: 540 AN: 2106

Alfa AF: 0.313 Hom.: 7562

Bravo AF: 0.246

Asia WGS AF: 0.170 AC: 594 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

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	0.22
DANN	Benign	0.61
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs17501521; hg19: chr11-67224988; COSMIC: COSV56886794; COSMIC: COSV56886794;