Variant chr12-120640812-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001033677.2(CABP1):c.127A>T(p.Thr43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000925 in 1,088,682 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0045 ( 9 hom., cov: 31)

Exomes 𝑓: 0.00036 ( 3 hom. )

Consequence

CABP1
NM_001033677.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.277

Variant links:

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]

CABP1 links:

CABP1-DT (HGNC:55491): (CABP1 divergent transcript)

CABP1-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008601695).

BS2

High AC in GnomAd4 at 665 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CABP1	NM_001033677.2 linkuse as main transcript	c.127A>T	p.Thr43Ser	missense_variant	1/6	ENST00000316803.8	NP_001028849.1
CABP1	XM_017020235.2 linkuse as main transcript	c.127A>T	p.Thr43Ser	missense_variant	1/6		XP_016875724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABP1	ENST00000316803.8 linkuse as main transcript	c.127A>T	p.Thr43Ser	missense_variant	1/6	1	NM_001033677.2	ENSP00000317310		Q9NZU7-4
CABP1-DT	ENST00000540369.2 linkuse as main transcript	n.129+651T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00454

AC:

665

AN:

146606

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00283

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:

0.0000304

Gnomad OTH

AF:

0.00149

GnomAD4 exome

AF:

0.000363

AC:

342

AN:

941976

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

135

AN XY:

442818

show subpopulations

Gnomad4 AFR exome

AF:

0.0164

Gnomad4 AMR exome

AF:

0.00139

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000600

Gnomad4 OTH exome

AF:

0.000827

GnomAD4 genome

AF:

0.00453

AC:

665

AN:

146706

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

322

AN XY:

71540

show subpopulations

Gnomad4 AFR

AF:

0.0152

Gnomad4 AMR

AF:

0.00283

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000304

Gnomad4 OTH

AF:

0.00147

Alfa

AF:

0.0000717

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2023

The c.127A>T (p.T43S) alteration is located in exon 1 (coding exon 1) of the CABP1 gene. This alteration results from a A to T substitution at nucleotide position 127, causing the threonine (T) at amino acid position 43 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.72

DEOGEN2

Benign

0.0076

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.34

M_CAP

Pathogenic

0.61

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.050

REVEL

Benign

0.15

Sift

Benign

0.045

Sift4G

Benign

0.54

Polyphen

0.010

Vest4

0.14

MutPred

0.20

Gain of catalytic residue at P45 (P = 0);

MVP

0.49

MPC

1.0

ClinPred

0.039

GERP RS

-1.2

Varity_R

0.045

gMVP

0.18

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over