rs9434

Variant names:

• chr1-22647804-C-A
• rs9434
• NM_172369.5:c.*21C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-22647804-C-A
• chr1-22647804-C-G
• chr1-22647804-C-T

Variant summary

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

The NM_172369.5(C1QC):​c.*21C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,597,894 control chromosomes in the GnomAD database, including 138,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (22040 hom., cov: 30)
  • Exomes 𝑓: 0.39 (116309 hom.)
• Consequence: C1QC NM_172369.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.416
• Publications: 23 publications found

Genes affected

C1QC (HGNC:1245): (complement C1q C chain) This gene encodes the C-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]

C1QC Gene-Disease associations (from GenCC):

• C1Q deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000308848 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 1-22647804-C-A is Benign according to our data. Variant chr1-22647804-C-A is described in ClinVar as Benign. ClinVar VariationId is 1221376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1QC	NM_172369.5	c.*21C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000374640.9	NP_758957.2
C1QC	NM_001114101.3	c.*21C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001107573.1
C1QC	NM_001347619.2	c.*21C>A		3_prime_UTR_variant	Exon 3 of 3		NP_001334548.1
C1QC	NM_001347620.2	c.*21C>A		3_prime_UTR_variant	Exon 2 of 2		NP_001334549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9	c.*21C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_172369.5	ENSP00000363771.4

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76359 AN: 151326 Hom.: 22004 Cov.: 30

Gnomad AFR AF: 0.798

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.482

GnomAD2 exomes AF: 0.442 AC: 105279 AN: 238412 AF XY: 0.428

Gnomad AFR exome AF: 0.816

Gnomad AMR exome AF: 0.508

Gnomad ASJ exome AF: 0.337

Gnomad EAS exome AF: 0.588

Gnomad FIN exome AF: 0.378

Gnomad NFE exome AF: 0.369

Gnomad OTH exome AF: 0.413

GnomAD4 exome AF: 0.392 AC: 567574 AN: 1446450 Hom.: 116309 Cov.: 47 AF XY: 0.391 AC XY: 281471 AN XY: 719906

African (AFR) AF: 0.821 AC: 27455 AN: 33458

American (AMR) AF: 0.507 AC: 22652 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 8822 AN: 26134

East Asian (EAS) AF: 0.569 AC: 22585 AN: 39692

South Asian (SAS) AF: 0.415 AC: 35737 AN: 86212

European-Finnish (FIN) AF: 0.378 AC: 14785 AN: 39118

Middle Eastern (MID) AF: 0.371 AC: 1900 AN: 5126

European-Non Finnish (NFE) AF: 0.368 AC: 408690 AN: 1111794

Other (OTH) AF: 0.414 AC: 24948 AN: 60224

GnomAD4 genome AF: 0.505 AC: 76437 AN: 151444 Hom.: 22040 Cov.: 30 AF XY: 0.504 AC XY: 37295 AN XY: 74004

African (AFR) AF: 0.798 AC: 32916 AN: 41246

American (AMR) AF: 0.479 AC: 7299 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1166 AN: 3456

East Asian (EAS) AF: 0.573 AC: 2905 AN: 5068

South Asian (SAS) AF: 0.426 AC: 2041 AN: 4794

European-Finnish (FIN) AF: 0.360 AC: 3784 AN: 10522

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 24969 AN: 67824

Other (OTH) AF: 0.484 AC: 1018 AN: 2104

Alfa AF: 0.422 Hom.: 8236

Bravo AF: 0.530

Asia WGS AF: 0.525 AC: 1827 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	3.7
DANN	Benign	0.82
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9434; hg19: chr1-22974297; COSMIC: COSV65889466; COSMIC: COSV65889466;