1-22644029-C-T

Variant names:

• chr1-22644029-C-T
• rs148237661
• NM_172369.5:c.6C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_172369.5(C1QC):​c.6C>T​(p.Asp2Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,591,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: C1QC NM_172369.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.320
• Publications: 0 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

ENSG00000289692 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 1-22644029-C-T is Benign according to our data. Variant chr1-22644029-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1544198.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.32 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172369.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QC	NM_172369.5	MANE Select	c.6C>T	p.Asp2Asp	synonymous	Exon 2 of 3	NP_758957.2	P02747
	C1QC	NM_001114101.3		c.6C>T	p.Asp2Asp	synonymous	Exon 2 of 3	NP_001107573.1	P02747
	C1QC	NM_001347619.2		c.6C>T	p.Asp2Asp	synonymous	Exon 2 of 3	NP_001334548.1	P02747

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1QC	ENST00000374640.9	TSL:1 MANE Select	c.6C>T	p.Asp2Asp	synonymous	Exon 2 of 3	ENSP00000363771.4	P02747
	ENSG00000289692	ENST00000695747.1		c.591C>T	p.Asp197Asp	synonymous	Exon 5 of 5	ENSP00000512140.1	A0A8Q3SI62
	ENSG00000289692	ENST00000695748.1		c.511C>T	p.Arg171Cys	missense	Exon 4 of 4	ENSP00000512141.1	A0A8Q3SI77

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152018 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000951 AC: 20 AN: 210358 AF XY: 0.0000796

Gnomad AFR exome AF: 0.000231

Gnomad AMR exome AF: 0.0000670

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000323 AC: 465 AN: 1439376 Hom.: 0 Cov.: 31 AF XY: 0.000310 AC XY: 221 AN XY: 713538

African (AFR) AF: 0.0000900 AC: 3 AN: 33344

American (AMR) AF: 0.0000488 AC: 2 AN: 41012

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25424

East Asian (EAS) AF: 0.00 AC: 0 AN: 38992

South Asian (SAS) AF: 0.00 AC: 0 AN: 81972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4972

European-Non Finnish (NFE) AF: 0.000404 AC: 445 AN: 1102766

Other (OTH) AF: 0.000252 AC: 15 AN: 59546

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152018 Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74262

African (AFR) AF: 0.000121 AC: 5 AN: 41406

American (AMR) AF: 0.000327 AC: 5 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67972

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000988 Hom.: 0

Bravo AF: 0.000136

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.5
DANN	Benign	0.60
PhyloP100		-0.32
PromoterAI		-0.051	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs148237661; hg19: chr1-22970522;