rs9267663

Positions:

• chr6-31899476-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000695637.1(C2):​c.-360+1201C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 166,388 control chromosomes in the GnomAD database, including 660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.074 (642 hom., cov: 27)
  • Exomes 𝑓: 0.025 (18 hom.)
• Consequence: C2 ENST00000695637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

Genes affected

C2 (HGNC:1248): (complement C2) Component C2 is a serum glycoprotein that functions as part of the classical pathway of the complement system. Activated C1 cleaves C2 into C2a and C2b. The serine proteinase C2a then combines with complement factor 4b to create the C3 or C5 convertase. Deficiency of C2 has been reported to associated with certain autoimmune diseases and SNPs in this gene have been associated with altered susceptibility to age-related macular degeneration. This gene localizes within the class III region of the MHC on the short arm of chromosome 6. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants have been described in publications but their full-length sequence has not been determined.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2	NM_001282457.2	c.-64+1534C>T		intron_variant			NP_001269386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000469372.5	c.-64+1534C>T		intron_variant		2		ENSP00000418923
C2	ENST00000497706.6	c.-64+1534C>T		intron_variant		5		ENSP00000417482
C2	ENST00000695637.1	c.-360+1201C>T		intron_variant				ENSP00000512074

Frequencies

GnomAD3 genomes AF: 0.0737 AC: 11171 AN: 151676 Hom.: 643 Cov.: 27

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0862

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0506

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.00492

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0247 AC: 360 AN: 14592 Hom.: 18 AF XY: 0.0261 AC XY: 193 AN XY: 7394

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0481

Gnomad4 ASJ exome AF: 0.0426

Gnomad4 EAS exome AF: 0.00292

Gnomad4 SAS exome AF: 0.0643

Gnomad4 FIN exome AF: 0.00258

Gnomad4 NFE exome AF: 0.0179

Gnomad4 OTH exome AF: 0.0265

GnomAD4 genome AF: 0.0737 AC: 11180 AN: 151796 Hom.: 642 Cov.: 27 AF XY: 0.0723 AC XY: 5365 AN XY: 74210

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.00492

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0445 Hom.: 133

Bravo AF: 0.0827

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.99

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9267663; hg19: chr6-31867253;