rs3745746

Positions:

• chr19-48034328-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019855.5(CABP5):​c.383T>C​(p.Val128Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 1,597,842 control chromosomes in the GnomAD database, including 108,724 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.30 (7860 hom., cov: 30)
  • Exomes 𝑓: 0.37 (100864 hom.)
• Consequence: CABP5 NM_019855.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82

Genes affected

CABP5 (HGNC:13714): (calcium binding protein 5) The product of this gene belongs to a subfamily of calcium binding proteins, which share similarity to calmodulin. Calcium binding proteins are an important component of calcium mediated cellular signal transduction. Expression of this gene is retina-specific. The mouse homolog of this protein has been shown to express in the inner nuclear layer of the retina, suggested its role in neuronal functioning. The specific function of this gene is unknown. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010474622).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CABP5	NM_019855.5	c.383T>C	p.Val128Ala	missense_variant	5/6	ENST00000293255.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CABP5	ENST00000293255.3	c.383T>C	p.Val128Ala	missense_variant	5/6	1	NM_019855.5	P1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45914 AN: 151806 Hom.: 7863 Cov.: 30

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.0811

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.327

GnomAD3 exomes AF: 0.325 AC: 77428 AN: 238008 Hom.: 14096 AF XY: 0.337 AC XY: 43560 AN XY: 129172

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.444

Gnomad EAS exome AF: 0.0710

Gnomad SAS exome AF: 0.351

Gnomad FIN exome AF: 0.335

Gnomad NFE exome AF: 0.392

Gnomad OTH exome AF: 0.351

GnomAD4 exome AF: 0.367 AC: 530527 AN: 1445918 Hom.: 100864 Cov.: 33 AF XY: 0.368 AC XY: 264467 AN XY: 719042

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.432

Gnomad4 EAS exome AF: 0.115

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.334

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.356

GnomAD4 genome AF: 0.302 AC: 45914 AN: 151924 Hom.: 7860 Cov.: 30 AF XY: 0.301 AC XY: 22350 AN XY: 74266

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.0809

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.385

Gnomad4 OTH AF: 0.325

Alfa AF: 0.379 Hom.: 25318

Bravo AF: 0.290

TwinsUK AF: 0.379 AC: 1406

ALSPAC AF: 0.390 AC: 1502

ESP6500AA AF: 0.172 AC: 756

ESP6500EA AF: 0.388 AC: 3333

ExAC AF: 0.325 AC: 39458

Asia WGS AF: 0.201 AC: 701 AN: 3478

EpiCase AF: 0.399

EpiControl AF: 0.400

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.10
DANN	Benign	0.44
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.2	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	2.1	N
REVEL	Benign	0.075
Sift	Benign	1.0	T
Sift4G	Benign	0.98	T
Polyphen		0.0	B
Vest4		0.017
MPC		0.30
ClinPred		0.0012	T
GERP RS		-5.2
Varity_R		0.023
gMVP		0.21

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: rs3745746; hg19: chr19-48537585; COSMIC: COSV53152829;