17-5432890-T-C

Variant names:

• chr17-5432890-T-C
• rs1050461
• NM_001212.4:c.*125A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001212.4(C1QBP):​c.*125A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,131,202 control chromosomes in the GnomAD database, including 46,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5787 hom., cov: 32)
  • Exomes 𝑓: 0.26 (40939 hom.)
• Consequence: C1QBP NM_001212.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• Publications: 11 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]

RPAIN (HGNC:28641): (RPA interacting protein) Predicted to enable metal ion binding activity. Acts upstream of or within several processes, including DNA metabolic process; protein import into nucleus; and response to UV. Located in PML body; cytoplasm; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000263272 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-5432890-T-C is Benign according to our data. Variant chr17-5432890-T-C is described in ClinVar as Benign. ClinVar VariationId is 1286412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QBP	NM_001212.4	MANE Select	c.*125A>G		3_prime_UTR	Exon 6 of 6	NP_001203.1	Q07021
	RPAIN	NM_001033002.4	MANE Select	c.*319T>C		downstream_gene	N/A	NP_001028174.2	Q86UA6-1
	RPAIN	NM_001160244.2		c.*319T>C		downstream_gene	N/A	NP_001153716.1	Q86UA6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QBP	ENST00000225698.8	TSL:1 MANE Select	c.*125A>G		3_prime_UTR	Exon 6 of 6	ENSP00000225698.4	Q07021
	C1QBP	ENST00000574444.5	TSL:3	c.*125A>G		3_prime_UTR	Exon 6 of 6	ENSP00000460308.1	I3L3B0
	RPAIN	ENST00000381209.8	TSL:1 MANE Select	c.*319T>C		downstream_gene	N/A	ENSP00000370606.3	Q86UA6-1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36699 AN: 151776 Hom.: 5786 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.258 AC: 253033 AN: 979308 Hom.: 40939 Cov.: 13 AF XY: 0.264 AC XY: 128552 AN XY: 487112

African (AFR) AF: 0.129 AC: 2852 AN: 22184

American (AMR) AF: 0.376 AC: 7382 AN: 19652

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 4019 AN: 16936

East Asian (EAS) AF: 0.797 AC: 27958 AN: 35072

South Asian (SAS) AF: 0.466 AC: 23977 AN: 51506

European-Finnish (FIN) AF: 0.310 AC: 12441 AN: 40156

Middle Eastern (MID) AF: 0.248 AC: 729 AN: 2944

European-Non Finnish (NFE) AF: 0.217 AC: 162174 AN: 748132

Other (OTH) AF: 0.269 AC: 11501 AN: 42726

GnomAD4 genome AF: 0.242 AC: 36730 AN: 151894 Hom.: 5787 Cov.: 32 AF XY: 0.254 AC XY: 18853 AN XY: 74240

African (AFR) AF: 0.131 AC: 5438 AN: 41458

American (AMR) AF: 0.307 AC: 4692 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 806 AN: 3460

East Asian (EAS) AF: 0.798 AC: 4128 AN: 5170

South Asian (SAS) AF: 0.479 AC: 2299 AN: 4796

European-Finnish (FIN) AF: 0.331 AC: 3477 AN: 10496

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15170 AN: 67940

Other (OTH) AF: 0.255 AC: 539 AN: 2110

Alfa AF: 0.130 Hom.: 267

Bravo AF: 0.234

Asia WGS AF: 0.579 AC: 2010 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1050461; hg19: chr17-5336210;