chr12-7081476-GT-G

Position:

• chr12-7081476-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.1349-176delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0609 in 134,664 control chromosomes in the GnomAD database, including 259 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.061 (259 hom., cov: 30)
• Consequence: C1R NM_001733.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.715

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-7081476-GT-G is Benign according to our data. Variant chr12-7081476-GT-G is described in ClinVar as [Benign]. Clinvar id is 1289551.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1R	NM_001733.7	c.1349-176delA		intron_variant		ENST00000647956.2	NP_001724.4
C1R	NM_001354346.2	c.1391-176delA		intron_variant			NP_001341275.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1R	ENST00000647956.2	c.1349-176delA		intron_variant			NM_001733.7	ENSP00000497341.1

Frequencies

GnomAD3 genomes AF: 0.0609 AC: 8206 AN: 134660 Hom.: 260 Cov.: 30

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0805

Gnomad AMR AF: 0.0552

Gnomad ASJ AF: 0.0451

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.0989

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0500

Gnomad NFE AF: 0.0746

Gnomad OTH AF: 0.0643

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0609 AC: 8206 AN: 134664 Hom.: 259 Cov.: 30 AF XY: 0.0633 AC XY: 4117 AN XY: 65054

Gnomad4 AFR AF: 0.0175

Gnomad4 AMR AF: 0.0552

Gnomad4 ASJ AF: 0.0451

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.0993

Gnomad4 FIN AF: 0.120

Gnomad4 NFE AF: 0.0746

Gnomad4 OTH AF: 0.0670

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 20, 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: rs370513331; hg19: chr12-7188780;