dbSNP rs374614759: C1R:c.*50_*51delAA (chr12-7080480-GTT-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001733.7(C1R):c.*50_*51delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,077,518 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

C1R
NM_001733.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

0 publications found

Variant links:

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

C1R links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.50_51delAA		3_prime_UTR	Exon 11 of 11	NP_001724.4	A0A3B3ISR2
	C1R	NM_001354346.2		c.50_51delAA		3_prime_UTR	Exon 11 of 11	NP_001341275.1	B4DPQ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C1R	ENST00000647956.2	MANE Select	c.50_51delAA	3_prime_UTR	Exon 11 of 11	ENSP00000497341.1	A0A3B3ISR2
C1R	ENST00000649804.1		c.50_51delAA	splice_region	Exon 5 of 5	ENSP00000497938.1	A0A3B3ITU4
C1R	ENST00000903851.1		c.50_51delAA	3_prime_UTR	Exon 12 of 12	ENSP00000573910.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

146694

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000232

AC:

AN:

1077518

Hom.:

AF XY:

0.0000323

AC XY:

AN XY:

526780

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

23674

American (AMR)

AF:

0.00

AC:

AN:

22130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15924

East Asian (EAS)

AF:

0.000545

AC:

AN:

29368

South Asian (SAS)

AF:

0.0000363

AC:

AN:

55060

European-Finnish (FIN)

AF:

0.0000519

AC:

AN:

38554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4566

European-Non Finnish (NFE)

AF:

0.00000474

AC:

AN:

844286

Other (OTH)

AF:

0.0000228

AC:

AN:

43956

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000666991), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.373

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

146694

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71298

African (AFR)

AF:

0.00

AC:

AN:

40096

American (AMR)

AF:

0.00

AC:

AN:

14644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3406

East Asian (EAS)

AF:

0.00

AC:

AN:

5064

South Asian (SAS)

AF:

0.00

AC:

AN:

4628

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66276

Other (OTH)

AF:

0.00

AC:

AN:

2006

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over