17-5437730-G-C

Variant summary

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

The NM_001212.4(C1QBP):c.383+393C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,186 control chromosomes in the GnomAD database, including 2,576 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 0.13 (2576 hom., cov: 33)
• Consequence: C1QBP NM_001212.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.143

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QBP	NM_001212.4	c.383+393C>G		intron_variant		ENST00000225698.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QBP	ENST00000225698.8	c.383+393C>G		intron_variant		1	NM_001212.4	P1
C1QBP	ENST00000570805.1	c.71+393C>G		intron_variant		3
C1QBP	ENST00000574444.5	c.71+393C>G		intron_variant		3
C1QBP	ENST00000573406.1	n.465+393C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19885 AN: 152068 Hom.: 2585 Cov.: 33

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.131 AC: 19883 AN: 152186 Hom.: 2576 Cov.: 33 AF XY: 0.143 AC XY: 10646 AN XY: 74400

Gnomad4 AFR AF: 0.0232

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0694 Hom.: 97

Bravo AF: 0.122

Asia WGS AF: 0.449 AC: 1558 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.59
Dann	Benign	0.47

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: rs2472614; hg19: chr17-5341050;