17-5432868-A-G

Position:

• chr17-5432868-A-G

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.*147T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,003,352 control chromosomes in the GnomAD database, including 41,533 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5797 hom., cov: 32)
  • Exomes 𝑓: 0.26 (35736 hom.)
• Consequence: C1QBP NM_001212.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.15

Genes affected

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]

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 17-5432868-A-G is Benign according to our data. Variant chr17-5432868-A-G is described in ClinVar as [Benign]. Clinvar id is 1234192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPAIN	NM_001033002.4	c.*297A>G		3_prime_UTR_variant	7/7	ENST00000381209.8
C1QBP	NM_001212.4	c.*147T>C		3_prime_UTR_variant	6/6	ENST00000225698.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QBP	ENST00000225698.8	c.*147T>C		3_prime_UTR_variant	6/6	1	NM_001212.4	P1
RPAIN	ENST00000381209.8	c.*297A>G		3_prime_UTR_variant	7/7	1	NM_001033002.4	P1
	ENST00000575890.1	n.9T>C		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36716 AN: 152020 Hom.: 5796 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.256 AC: 217622 AN: 851214 Hom.: 35736 Cov.: 11 AF XY: 0.262 AC XY: 111261 AN XY: 424108

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.359

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.795

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.242 AC: 36747 AN: 152138 Hom.: 5797 Cov.: 32 AF XY: 0.254 AC XY: 18866 AN XY: 74378

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.255

Alfa AF: 0.238 Hom.: 613

Bravo AF: 0.234

Asia WGS AF: 0.580 AC: 2009 AN: 3474

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	-0.86
CADD	Benign	5.8
DANN	Benign	0.62
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: rs1050456; hg19: chr17-5336188;