12-120646851-C-A

Position:

• chr12-120646851-C-A

Variant summary

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

The NM_001033677.2(CABP1):​c.654+5512C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,048 control chromosomes in the GnomAD database, including 11,969 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 0.39 (11969 hom., cov: 32)
• Consequence: CABP1 NM_001033677.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0110

Genes affected

CABP1 (HGNC:1384): (calcium binding protein 1) Calcium binding proteins are an important component of calcium mediated cellular signal transduction. This gene encodes a protein that belongs to a subfamily of calcium binding proteins which share similarity to calmodulin. The protein encoded by this gene regulates the gating of voltage-gated calcium ion channels. This protein inhibits calcium-dependent inactivation and supports calcium-dependent facilitation of ion channels containing voltage-dependent L-type calcium channel subunit alpha-1C. This protein also regulates calcium-dependent activity of inositol 1,4,5-triphosphate receptors, P/Q-type voltage-gated calcium channels, and transient receptor potential channel TRPC5. This gene is predominantly expressed in retina and brain. Alternative splicing results in multiple transcript variants encoding disinct isoforms. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABP1	NM_001033677.2	c.654+5512C>A		intron_variant		ENST00000316803.8	NP_001028849.1
CABP1	XM_017020235.2	c.654+5512C>A		intron_variant			XP_016875724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABP1	ENST00000316803.8	c.654+5512C>A		intron_variant		1	NM_001033677.2	ENSP00000317310

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59742 AN: 151930 Hom.: 11974 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.389

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

GnomAD4 genome AF: 0.393 AC: 59743 AN: 152048 Hom.: 11969 Cov.: 32 AF XY: 0.389 AC XY: 28881 AN XY: 74320

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.386

Alfa AF: 0.406 Hom.: 1897

Bravo AF: 0.392

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.2
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1168070; hg19: chr12-121084654;