Variant chr17-5433172-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001212.4(C1QBP):c.700-8C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00519 in 1,610,432 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0053 ( 27 hom. )

Consequence

C1QBP
NM_001212.4 splice_region, intron

Scores

Splicing: ADA: 0.002874

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.839

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:

C1QBP (HGNC:):

C1QBP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 17-5433172-G-T is Benign according to our data. Variant chr17-5433172-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 711527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00443 (674/152172) while in subpopulation NFE AF= 0.00647 (440/67992). AF 95% confidence interval is 0.00597. There are 4 homozygotes in gnomad4. There are 329 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QBP	NM_001212.4 linkuse as main transcript	c.700-8C>A		splice_region_variant, intron_variant		ENST00000225698.8	NP_001203.1	Q07021

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QBP	ENST00000225698.8 linkuse as main transcript	c.700-8C>A		splice_region_variant, intron_variant		1	NM_001212.4	ENSP00000225698.4		Q07021

Frequencies

GnomAD3 genomes

AF:

0.00444

AC:

675

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000918

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.0159

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00840

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00647

Gnomad OTH

AF:

0.00432

GnomAD3 exomes

AF:

0.00482

AC:

1189

AN:

246870

Hom.:

AF XY:

0.00482

AC XY:

645

AN XY:

133746

show subpopulations

Gnomad AFR exome

AF:

0.000824

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000707

Gnomad FIN exome

AF:

0.00677

Gnomad NFE exome

AF:

0.00648

Gnomad OTH exome

AF:

0.00533

GnomAD4 exome

AF:

0.00527

AC:

7692

AN:

1458260

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

3823

AN XY:

725434

show subpopulations

Gnomad4 AFR exome

AF:

0.00118

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00108

Gnomad4 FIN exome

AF:

0.00671

Gnomad4 NFE exome

AF:

0.00567

Gnomad4 OTH exome

AF:

0.00546

GnomAD4 genome

AF:

0.00443

AC:

674

AN:

152172

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000915

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.0159

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00840

Gnomad4 NFE

AF:

0.00647

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00514

Hom.:

Bravo

AF:

0.00377

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	C1QBP: BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

C1QBP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 16, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.6

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0029

dbscSNV1_RF

Benign

0.11

SpliceAI score (max)

0.010

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