rs544167

Positions:

• chr6-31922381-T-G

Variant summary

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

The ENST00000695637.1(C2):​c.-359-5574T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0715 in 152,146 control chromosomes in the GnomAD database, including 413 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 0.072 (413 hom., cov: 32)
• Consequence: C2 ENST00000695637.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) 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
C2	NM_001178063.3	c.74-11229T>G		intron_variant			NP_001171534.1
C2	NM_001282457.2	c.-63-11229T>G		intron_variant			NP_001269386.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000413154.5	c.-100+2355T>G		intron_variant		4		ENSP00000403325
C2	ENST00000452202.5	c.74-11229T>G		intron_variant		4		ENSP00000406121
C2	ENST00000452323.7	c.74-11229T>G		intron_variant		2		ENSP00000392322

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10869 AN: 152028 Hom.: 412 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0810

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

GnomAD4 genome AF: 0.0715 AC: 10882 AN: 152146 Hom.: 413 Cov.: 32 AF XY: 0.0686 AC XY: 5104 AN XY: 74370

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.00501

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0660

Gnomad4 OTH AF: 0.0802

Alfa AF: 0.0553 Hom.: 157

Bravo AF: 0.0772

Asia WGS AF: 0.0150 AC: 51 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.0
DANN	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs544167; hg19: chr6-31890158;