17-5433077-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001212.4(C1QBP):c.787C>G(p.Leu263Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L263L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

C1QBP
NM_001212.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Variant links:

Genes affected

C1QBP (HGNC:1243): (complement C1q binding protein) The human complement subcomponent C1q associates with C1r and C1s in order to yield the first component of the serum complement system. The protein encoded by this gene is known to bind to the globular heads of C1q molecules and inhibit C1 activation. This protein has also been identified as the p32 subunit of pre-mRNA splicing factor SF2, as well as a hyaluronic acid-binding protein. [provided by RefSeq, Jul 2008]

C1QBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20253053).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QBP	NM_001212.4 linkuse as main transcript	c.787C>G	p.Leu263Val	missense_variant	6/6	ENST00000225698.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
C1QBP	ENST00000225698.8 linkuse as main transcript	c.787C>G	p.Leu263Val	missense_variant	6/6	1	NM_001212.4	P1
C1QBP	ENST00000574444.5 linkuse as main transcript	c.475C>G	p.Leu159Val	missense_variant	6/6	3
C1QBP	ENST00000570805.1 linkuse as main transcript	c.475C>G	p.Leu159Val	missense_variant	6/6	3
C1QBP	ENST00000573204.1 linkuse as main transcript	n.906C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251380

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Jun 16, 2022

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 263 of the C1QBP protein (p.Leu263Val). This variant is present in population databases (rs772737093, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with C1QBP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.45

Cadd

Benign

Dann

Benign

0.95

DEOGEN2

Benign

0.30

T;.;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

T;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.20

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.51

N;.;.

REVEL

Benign

0.031

Sift

Benign

0.48

T;.;.

Sift4G

Benign

0.24

T;T;.

Polyphen

0.30

B;.;.

Vest4

0.12

MutPred

0.47

Gain of glycosylation at S260 (P = 0.086);.;.;

MVP

0.18

MPC

0.71

ClinPred

0.11

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.49

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

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