NM_001212.4:c.233-281A>G

Variant names:

• chr17-5438554-T-C
• rs1805429
• NM_001212.4:c.233-281A>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.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
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001212.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QBP	NM_001212.4	MANE Select	c.233-281A>G		intron	N/A	NP_001203.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QBP	ENST00000225698.8	TSL:1 MANE Select	c.233-281A>G		intron	N/A	ENSP00000225698.4
	C1QBP	ENST00000576122.1	TSL:3	c.-143A>G		5_prime_UTR	Exon 1 of 2	ENSP00000458624.1
	C1QBP	ENST00000574444.5	TSL:3	c.-81+155A>G		intron	N/A	ENSP00000460308.1

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

African (AFR) AF: 0.0957 AC: 1318 AN: 13772

American (AMR) AF: 0.0490 AC: 809 AN: 16520

Ashkenazi Jewish (ASJ) AF: 0.0615 AC: 858 AN: 13954

East Asian (EAS) AF: 0.200 AC: 5892 AN: 29506

South Asian (SAS) AF: 0.175 AC: 7861 AN: 44888

European-Finnish (FIN) AF: 0.110 AC: 3114 AN: 28284

Middle Eastern (MID) AF: 0.0972 AC: 209 AN: 2150

European-Non Finnish (NFE) AF: 0.0661 AC: 24931 AN: 377324

Other (OTH) AF: 0.0886 AC: 2586 AN: 29194

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

African (AFR) AF: 0.100 AC: 4152 AN: 41526

American (AMR) AF: 0.0592 AC: 905 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0666 AC: 231 AN: 3468

East Asian (EAS) AF: 0.194 AC: 1003 AN: 5164

South Asian (SAS) AF: 0.182 AC: 878 AN: 4820

European-Finnish (FIN) AF: 0.118 AC: 1253 AN: 10596

Middle Eastern (MID) AF: 0.0719 AC: 21 AN: 292

European-Non Finnish (NFE) AF: 0.0669 AC: 4549 AN: 68014

Other (OTH) AF: 0.0871 AC: 184 AN: 2112

Alfa AF: 0.0693 Hom.: 497

Bravo AF: 0.0823

Asia WGS AF: 0.205 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.5
DANN	Benign	0.50
PhyloP100		0.20
PromoterAI		0.049	Neutral
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: rs1805429; hg19: chr17-5341874;