12-7080480-GT-G

Position:

• chr12-7080480-GT-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1R	NM_001733.7	c.*51delA		3_prime_UTR_variant	11/11	ENST00000647956.2	NP_001724.4
C1R	NM_001354346.2	c.*51delA		3_prime_UTR_variant	11/11		NP_001341275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1R	ENST00000647956	c.*51delA		3_prime_UTR_variant	11/11		NM_001733.7	ENSP00000497341.1

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

Gnomad4 AFR exome AF: 0.0856

Gnomad4 AMR exome AF: 0.0664

Gnomad4 ASJ exome AF: 0.156

Gnomad4 EAS exome AF: 0.0453

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0778

Gnomad4 NFE exome AF: 0.0775

Gnomad4 OTH exome AF: 0.0925

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

Gnomad4 AFR AF: 0.0669

Gnomad4 AMR AF: 0.0656

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.0576

Gnomad4 SAS AF: 0.0963

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.0635

Gnomad4 OTH AF: 0.0915

Bravo AF: 0.0645

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs374614759; hg19: chr12-7187784;