12-7090267-G-T

Position:

• chr12-7090267-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001733.7(C1R):​c.232-19C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 718,564 control chromosomes in the GnomAD database, including 2,149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (1495 hom., cov: 32)
  • Exomes 𝑓: 0.012 (654 hom.)
• Consequence: C1R NM_001733.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.645

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-7090267-G-T is Benign according to our data. Variant chr12-7090267-G-T is described in ClinVar as [Benign]. Clinvar id is 1294595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1R	NM_001733.7	c.232-19C>A		intron_variant		ENST00000647956.2
C1R	NM_001354346.2	c.274-19C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1R	ENST00000647956.2	c.232-19C>A		intron_variant			NM_001733.7	P1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11659 AN: 152002 Hom.: 1487 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00657

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0627

GnomAD3 exomes AF: 0.0191 AC: 3003 AN: 157584 Hom.: 352 AF XY: 0.0144 AC XY: 1202 AN XY: 83232

Gnomad AFR exome AF: 0.285

Gnomad AMR exome AF: 0.0140

Gnomad ASJ exome AF: 0.00624

Gnomad EAS exome AF: 0.00205

Gnomad SAS exome AF: 0.000706

Gnomad FIN exome AF: 0.0000616

Gnomad NFE exome AF: 0.00124

Gnomad OTH exome AF: 0.0105

GnomAD4 exome AF: 0.0125 AC: 7079 AN: 566444 Hom.: 654 Cov.: 0 AF XY: 0.0102 AC XY: 3116 AN XY: 305600

Gnomad4 AFR exome AF: 0.275

Gnomad4 AMR exome AF: 0.0156

Gnomad4 ASJ exome AF: 0.00629

Gnomad4 EAS exome AF: 0.0284

Gnomad4 SAS exome AF: 0.000874

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.000957

Gnomad4 OTH exome AF: 0.0225

GnomAD4 genome AF: 0.0769 AC: 11693 AN: 152120 Hom.: 1495 Cov.: 32 AF XY: 0.0746 AC XY: 5551 AN XY: 74386

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.0294

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00658

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.00635 Hom.: 27

Bravo AF: 0.0873

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4600291; hg19: chr12-7242863;