chr12-7089708-G-C

Variant names:

• chr12-7089708-G-C
• rs760553459
• NM_001733.7:c.450C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001733.7(C1R):​c.450C>G​(p.Ser150Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000318 in 628,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: C1R NM_001733.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.686

Genes affected

C1R (HGNC:1246): (complement C1r) This gene encodes a member of the peptidase S1 protein family. The encoded protein is a proteolytic subunit in the complement system C1 complex. The complement system acts as a mediator in the innate immune response by ultimately triggering phagocytosis, inflammation, and rupturing the bacterial cell wall. Mutations in this gene are associated with Ehlers-Danlos Syndrome. [provided by RefSeq, Dec 2018]

C1RL (HGNC:21265): (complement C1r subcomponent like) Predicted to enable serine-type endopeptidase activity. Predicted to be involved in zymogen activation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.099276096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C1R	NM_001733.7	c.450C>G	p.Ser150Arg	missense_variant	Exon 4 of 11	ENST00000647956.2	NP_001724.4
C1R	NM_001354346.2	c.492C>G	p.Ser164Arg	missense_variant	Exon 4 of 11		NP_001341275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1R	ENST00000647956.2	c.450C>G	p.Ser150Arg	missense_variant	Exon 4 of 11		NM_001733.7	ENSP00000497341.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000803 AC: 2 AN: 249022 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135086

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000318 AC: 2 AN: 628522 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 342396

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000457

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	8.6
DANN	Benign	0.79
DEOGEN2	Benign	0.026	.;.;T;T;T;.;T;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.59	T;.;T;T;T;T;T;T
MetaRNN	Benign	0.099	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.43	T
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.8	.;.;N;N;N;N;N;N
REVEL	Benign	0.16
Sift	Benign	0.62	.;.;T;T;T;T;T;T
Sift4G	Benign	0.54	.;.;T;.;.;.;.;T
Polyphen		0.011, 0.0020	.;.;B;B;.;.;.;.
Vest4		0.13, 0.17
MutPred		0.32		Loss of glycosylation at S150 (P = 0.0402);Loss of glycosylation at S150 (P = 0.0402);.;.;.;.;.;.;
MVP		0.83
ClinPred		0.043	T
GERP RS		4.4
gMVP		0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs760553459; hg19: chr12-7242304;