dbSNP rs9434: C1QC:c.*21C>A (chr1-22647804-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.416

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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	Effect	Exon rank	MANE	Protein	UniProt
C1QC	NM_172369.5 link	c.*21C>A	3_prime_UTR_variant	Exon 3 of 3	ENST00000374640.9	NP_758957.2	P02747A0A024RAA7
C1QC	NM_001114101.3 link	c.*21C>A	3_prime_UTR_variant	Exon 3 of 3		NP_001107573.1	P02747A0A024RAA7
C1QC	NM_001347619.2 link	c.*21C>A	3_prime_UTR_variant	Exon 3 of 3		NP_001334548.1	P02747A0A024RAA7
C1QC	NM_001347620.2 link	c.*21C>A	3_prime_UTR_variant	Exon 2 of 2		NP_001334549.1	A0A8Q3SIZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QC	ENST00000374640.9 link	c.*21C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_172369.5	ENSP00000363771.4		P02747

Frequencies

GnomAD3 genomes

AF:

0.505

AC:

76359

AN:

151326

Hom.:

22004

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.442

AC:

105279

AN:

238412

Hom.:

25124

AF XY:

0.428

AC XY:

55529

AN XY:

129708

show subpopulations

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 SAS exome

AF:

0.417

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.:

AF XY:

0.391

AC XY:

281471

AN XY:

719906

show subpopulations

Gnomad4 AFR exome

AF:

0.821

Gnomad4 AMR exome

AF:

0.507

Gnomad4 ASJ exome

AF:

0.338

Gnomad4 EAS exome

AF:

0.569

Gnomad4 SAS exome

AF:

0.415

Gnomad4 FIN exome

AF:

0.378

Gnomad4 NFE exome

AF:

0.368

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.505

AC:

76437

AN:

151444

Hom.:

22040

Cov.:

AF XY:

0.504

AC XY:

37295

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.798

Gnomad4 AMR

AF:

0.479

Gnomad4 ASJ

AF:

0.337

Gnomad4 EAS

AF:

0.573

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.360

Gnomad4 NFE

AF:

0.368

Gnomad4 OTH

AF:

0.484

Alfa

AF:

0.417

Hom.:

4909

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

LINK: link

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over