rs1805429

Positions:

• chr17-5438554-T-C

Variant summary

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

The NM_001212.4(C1QBP):​c.233-281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 707,792 control chromosomes in the GnomAD database, including 3,360 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 0.087 (702 hom., cov: 33)
  • Exomes 𝑓: 0.086 (2658 hom.)
• Consequence: C1QBP NM_001212.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.202

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QBP	NM_001212.4	c.233-281A>G		intron_variant		ENST00000225698.8	NP_001203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QBP	ENST00000225698.8	c.233-281A>G		intron_variant		1	NM_001212.4	ENSP00000225698	P1

Frequencies

GnomAD3 genomes AF: 0.0867 AC: 13179 AN: 152082 Hom.: 699 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0593

Gnomad ASJ AF: 0.0666

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0669

Gnomad OTH AF: 0.0804

GnomAD4 exome AF: 0.0856 AC: 47578 AN: 555592 Hom.: 2658 Cov.: 7 AF XY: 0.0898 AC XY: 25709 AN XY: 286406

Gnomad4 AFR exome AF: 0.0957

Gnomad4 AMR exome AF: 0.0490

Gnomad4 ASJ exome AF: 0.0615

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0661

Gnomad4 OTH exome AF: 0.0886

GnomAD4 genome AF: 0.0867 AC: 13197 AN: 152200 Hom.: 702 Cov.: 33 AF XY: 0.0916 AC XY: 6816 AN XY: 74428

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.0592

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.0669

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.0680 Hom.: 349

Bravo AF: 0.0823

Asia WGS AF: 0.205 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.5
DANN	Benign	0.50

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

Other links and lift over

dbSNP: rs1805429; hg19: chr17-5341874;