12-7080480-GTT-GT

Variant names:

• chr12-7080480-GT-G
• rs374614759
• NM_001733.7:c.*51delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001733.7(C1R):​c.*51delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0784 in 1,205,182 control chromosomes in the GnomAD database, including 1,840 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (310 hom., cov: 31)
  • Exomes 𝑓: 0.080 (1530 hom.)
• Consequence: C1R NM_001733.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• 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]

C1R Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, periodontal type 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• autosomal systemic lupus erythematosus type 16

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Ehlers-Danlos syndrome, periodontitis type

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 12-7080480-GT-G is Benign according to our data. Variant chr12-7080480-GT-G is described in ClinVar as Benign. ClinVar VariationId is 1246105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0889 is higher than 0.05.

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.*51delA		3_prime_UTR	Exon 11 of 11	NP_001724.4	A0A3B3ISR2
	C1R	NM_001354346.2		c.*51delA		3_prime_UTR	Exon 11 of 11	NP_001341275.1	B4DPQ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1R	ENST00000647956.2	MANE Select	c.*51delA		3_prime_UTR	Exon 11 of 11	ENSP00000497341.1	A0A3B3ISR2
	C1R	ENST00000649804.1		c.*51delA		splice_region	Exon 5 of 5	ENSP00000497938.1	A0A3B3ITU4
	C1R	ENST00000903851.1		c.*51delA		3_prime_UTR	Exon 12 of 12	ENSP00000573910.1

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 9846 AN: 146646 Hom.: 310 Cov.: 31

Gnomad AFR AF: 0.0669

Gnomad AMI AF: 0.0535

Gnomad AMR AF: 0.0657

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0575

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0912

GnomAD4 exome AF: 0.0800 AC: 84667 AN: 1058462 Hom.: 1530 Cov.: 32 AF XY: 0.0808 AC XY: 41805 AN XY: 517372

African (AFR) AF: 0.0856 AC: 1988 AN: 23218

American (AMR) AF: 0.0664 AC: 1427 AN: 21506

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 2434 AN: 15614

East Asian (EAS) AF: 0.0453 AC: 1290 AN: 28476

South Asian (SAS) AF: 0.106 AC: 5705 AN: 53830

European-Finnish (FIN) AF: 0.0778 AC: 2906 AN: 37342

Middle Eastern (MID) AF: 0.126 AC: 569 AN: 4502

European-Non Finnish (NFE) AF: 0.0775 AC: 64357 AN: 830840

Other (OTH) AF: 0.0925 AC: 3991 AN: 43134

GnomAD4 genome AF: 0.0672 AC: 9853 AN: 146720 Hom.: 310 Cov.: 31 AF XY: 0.0681 AC XY: 4862 AN XY: 71358

African (AFR) AF: 0.0669 AC: 2688 AN: 40178

American (AMR) AF: 0.0656 AC: 962 AN: 14656

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 454 AN: 3406

East Asian (EAS) AF: 0.0576 AC: 291 AN: 5048

South Asian (SAS) AF: 0.0963 AC: 445 AN: 4620

European-Finnish (FIN) AF: 0.0586 AC: 549 AN: 9364

Middle Eastern (MID) AF: 0.0951 AC: 27 AN: 284

European-Non Finnish (NFE) AF: 0.0635 AC: 4204 AN: 66244

Other (OTH) AF: 0.0915 AC: 185 AN: 2022

Alfa AF: 0.0206 Hom.: 12

Bravo AF: 0.0645

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		0.0

Splicing

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

Other links and lift over

dbSNP: rs374614759; hg19: chr12-7187784; COSMIC: COSV73383019;