chr19-48040605-G-C

Position:

• chr19-48040605-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019855.5(CABP5):​c.238C>G​(p.Leu80Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L80P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: CABP5 NM_019855.5 missense, splice_region
• Scores: Splicing: ADA: 0.00005603
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40431154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABP5	NM_019855.5	c.238C>G	p.Leu80Val	missense_variant, splice_region_variant	3/6	ENST00000293255.3	NP_062829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABP5	ENST00000293255.3	c.238C>G	p.Leu80Val	missense_variant, splice_region_variant	3/6	1	NM_019855.5	ENSP00000293255.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151932 Hom.: 0 Cov.: 30 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 47

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151932 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74186

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	9.0
DANN	Benign	0.81
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.63
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.95	N
REVEL	Benign	0.090
Sift	Benign	0.57	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.21
MutPred		0.55		Gain of catalytic residue at G81 (P = 0.2437);
MVP		0.14
MPC		0.25
ClinPred		0.16	T
GERP RS		-3.5
Varity_R		0.063
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000056
dbscSNV1_RF	Benign	0.018
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: rs8105198; hg19: chr19-48543862;