12-7091595-T-A

Position:

• chr12-7091595-T-A

Variant summary

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

The NM_001733.7(C1R):​c.88A>T​(p.Thr30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: C1R NM_001733.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.45

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1R	NM_001733.7	c.88A>T	p.Thr30Ser	missense_variant	2/11	ENST00000647956.2	NP_001724.4
C1R	NM_001354346.2	c.130A>T	p.Thr44Ser	missense_variant	2/11		NP_001341275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1R	ENST00000647956.2	c.88A>T	p.Thr30Ser	missense_variant	2/11		NM_001733.7	ENSP00000497341	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

C1R: PM2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	.;.;T;T;.;.
Eigen	Uncertain	0.19
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.55	T;.;T;T;T;T
MetaRNN	Uncertain	0.46	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.99	D;D;D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	.;.;N;N;N;D
REVEL	Benign	0.052
Sift	Benign	0.30	.;.;T;T;T;T
Sift4G	Benign	0.63	.;.;T;.;.;.
Polyphen		0.55, 0.90	.;.;P;P;.;.
Vest4		0.33, 0.34
MutPred		0.67		Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);.;Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);Gain of disorder (P = 0.0426);
MVP		0.20
ClinPred		0.97	D
GERP RS		5.3
gMVP		0.21

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-7244191;