1-22659522-C-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001378156.1(C1QB):c.60C>A(p.Ile20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,614,028 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. I20I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0086 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (24 hom.)
• Consequence: C1QB NM_001378156.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.53

Genes affected

C1QB (HGNC:1242): (complement C1q B chain) This gene encodes the B-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q is composed of 18 polypeptide chains which include 6 A-chains, 6 B-chains, and 6 C-chains. Each chain contains an N-terminal collagen-like region and a C-terminal C1q globular domain. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 1-22659522-C-A is Benign according to our data. Variant chr1-22659522-C-A is described in ClinVar as [Benign]. Clinvar id is 775523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.53 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00859 (1307/152200) while in subpopulation AFR AF= 0.0302 (1254/41498). AF 95% confidence interval is 0.0288. There are 23 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QB	NM_001378156.1	c.60C>A	p.Ile20=	synonymous_variant	2/3	ENST00000509305.6
C1QB	NM_000491.5	c.66C>A	p.Ile22=	synonymous_variant	2/3
C1QB	NM_001371184.3	c.60C>A	p.Ile20=	synonymous_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QB	ENST00000509305.6	c.60C>A	p.Ile20=	synonymous_variant	2/3	1	NM_001378156.1	P2

Frequencies

GnomAD3 genomes AF: 0.00857 AC: 1304 AN: 152082 Hom.: 24 Cov.: 32

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00227 AC: 571 AN: 251338 Hom.: 10 AF XY: 0.00163 AC XY: 222 AN XY: 135840

Gnomad AFR exome AF: 0.0317

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000907 AC: 1326 AN: 1461828 Hom.: 24 Cov.: 32 AF XY: 0.000806 AC XY: 586 AN XY: 727216

Gnomad4 AFR exome AF: 0.0319

Gnomad4 AMR exome AF: 0.000984

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000468

Gnomad4 OTH exome AF: 0.00229

GnomAD4 genome AF: 0.00859 AC: 1307 AN: 152200 Hom.: 23 Cov.: 32 AF XY: 0.00841 AC XY: 626 AN XY: 74404

Gnomad4 AFR AF: 0.0302

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.000592 Hom.: 0

Bravo AF: 0.00982

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

C1QB-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.11
Dann	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77379868; hg19: chr1-22986015;