chr17-5432890-T-C

Position:

• chr17-5432890-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1QBP	NM_001212.4	c.*125A>G		3_prime_UTR_variant	6/6	ENST00000225698.8	NP_001203.1
RPAIN	NM_001033002.4	c.*319T>C		downstream_gene_variant		ENST00000381209.8	NP_001028174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1QBP	ENST00000225698.8	c.*125A>G		3_prime_UTR_variant	6/6	1	NM_001212.4	ENSP00000225698.4
RPAIN	ENST00000381209.8	c.*319T>C		downstream_gene_variant		1	NM_001033002.4	ENSP00000370606.3

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

Gnomad4 AFR exome AF: 0.129

Gnomad4 AMR exome AF: 0.376

Gnomad4 ASJ exome AF: 0.237

Gnomad4 EAS exome AF: 0.797

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.269

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

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.479

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.255

Alfa AF: 0.130 Hom.: 260

Bravo AF: 0.234

Asia WGS AF: 0.579 AC: 2010 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1050461; hg19: chr17-5336210;