17-5432895-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001212.4(C1QBP):c.*119_*120insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,222,068 control chromosomes in the GnomAD database, including 434 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (43 hom., cov: 32)
  • Exomes 𝑓: 0.023 (391 hom.)
• Consequence: C1QBP NM_001212.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.146

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-5432895-A-AT is Benign according to our data. Variant chr17-5432895-A-AT is described in ClinVar as [Benign]. Clinvar id is 1283700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0194 (2948/152228) while in subpopulation SAS AF= 0.039 (188/4820). AF 95% confidence interval is 0.0344. There are 43 homozygotes in gnomad4. There are 1510 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QBP	NM_001212.4	c.*119_*120insA		3_prime_UTR_variant	6/6	ENST00000225698.8
RPAIN	NM_001033002.4			downstream_gene_variant		ENST00000381209.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QBP	ENST00000225698.8	c.*119_*120insA		3_prime_UTR_variant	6/6	1	NM_001212.4	P1
RPAIN	ENST00000381209.8			downstream_gene_variant		1	NM_001033002.4	P1
	ENST00000575890.1			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2946 AN: 152110 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.00512

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0166

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0392

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.0478

Gnomad NFE AF: 0.0226

Gnomad OTH AF: 0.0192

GnomAD4 exome AF: 0.0230 AC: 24592 AN: 1069840 Hom.: 391 Cov.: 14 AF XY: 0.0235 AC XY: 12454 AN XY: 529968

Gnomad4 AFR exome AF: 0.00475

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.0399

Gnomad4 EAS exome AF: 0.000139

Gnomad4 SAS exome AF: 0.0377

Gnomad4 FIN exome AF: 0.0455

Gnomad4 NFE exome AF: 0.0222

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0194 AC: 2948 AN: 152228 Hom.: 43 Cov.: 32 AF XY: 0.0203 AC XY: 1510 AN XY: 74434

Gnomad4 AFR AF: 0.00515

Gnomad4 AMR AF: 0.0166

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0390

Gnomad4 FIN AF: 0.0490

Gnomad4 NFE AF: 0.0226

Gnomad4 OTH AF: 0.0190

Bravo AF: 0.0159

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs41307958; hg19: chr17-5336215;