NM_001733.7:c.425-14T>G

Variant names:

• chr12-7089747-A-C
• rs1470834335
• NM_001733.7:c.425-14T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001733.7(C1R):​c.425-14T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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)
• Consequence: C1R NM_001733.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001733.7. 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
	C1R	NM_001733.7	MANE Select	c.425-14T>G		intron	N/A	NP_001724.4	A0A3B3ISR2
	C1R	NM_001354346.2		c.467-14T>G		intron	N/A	NP_001341275.1	B4DPQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1R	ENST00000647956.2	MANE Select	c.425-14T>G		intron	N/A	ENSP00000497341.1	A0A3B3ISR2
	C1R	ENST00000903851.1		c.578-14T>G		intron	N/A	ENSP00000573910.1
	C1R	ENST00000903850.1		c.497-14T>G		intron	N/A	ENSP00000573909.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.5
DANN	Benign	0.83
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs1470834335; hg19: chr12-7242343;