17-5437730-G-C

Variant names:

• chr17-5437730-G-C
• rs2472614
• NM_001212.4:c.383+393C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• combined oxidative phosphorylation deficiency 33

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
C1QBP	NM_001212.4	c.383+393C>G		intron_variant	Intron 2 of 5	ENST00000225698.8	NP_001203.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QBP	ENST00000225698.8	c.383+393C>G		intron_variant	Intron 2 of 5	1	NM_001212.4	ENSP00000225698.4
C1QBP	ENST00000574444.5	c.71+393C>G		intron_variant	Intron 2 of 5	3		ENSP00000460308.1
C1QBP	ENST00000570805.1	c.71+393C>G		intron_variant	Intron 2 of 5	3		ENSP00000460638.1
C1QBP	ENST00000573406.1	n.465+393C>G		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.0232 AC: 962 AN: 41548

American (AMR) AF: 0.191 AC: 2924 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3364 AN: 5170

South Asian (SAS) AF: 0.321 AC: 1551 AN: 4826

European-Finnish (FIN) AF: 0.248 AC: 2621 AN: 10568

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7657 AN: 67994

Other (OTH) AF: 0.130 AC: 274 AN: 2114

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
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2472614; hg19: chr17-5341050;