rs497239

Variant names:

• chr6-31940984-T-C
• rs497239
• NM_000063.6:c.1219+1664T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000063.6(C2):​c.1219+1664T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,174 control chromosomes in the GnomAD database, including 1,220 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 0.12 (1220 hom., cov: 32)
• Consequence: C2 NM_000063.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 19 publications found

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]

ENSG00000244255 (HGNC:):

C2-AS1 (HGNC:49464): (C2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2	NM_000063.6	c.1219+1664T>C		intron_variant	Intron 9 of 17	ENST00000299367.10	NP_000054.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2	ENST00000299367.10	c.1219+1664T>C		intron_variant	Intron 9 of 17	1	NM_000063.6	ENSP00000299367.5
ENSG00000244255	ENST00000456570.5	c.760+1664T>C		intron_variant	Intron 6 of 29	2		ENSP00000410815.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17801 AN: 152056 Hom.: 1222 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0574

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0574

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.117 AC: 17822 AN: 152174 Hom.: 1220 Cov.: 32 AF XY: 0.115 AC XY: 8555 AN XY: 74412

African (AFR) AF: 0.191 AC: 7936 AN: 41478

American (AMR) AF: 0.101 AC: 1545 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0574 AC: 199 AN: 3468

East Asian (EAS) AF: 0.0593 AC: 307 AN: 5180

South Asian (SAS) AF: 0.142 AC: 683 AN: 4820

European-Finnish (FIN) AF: 0.0574 AC: 609 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0911 AC: 6193 AN: 68012

Other (OTH) AF: 0.132 AC: 280 AN: 2116

Alfa AF: 0.0910 Hom.: 1169

Bravo AF: 0.124

Asia WGS AF: 0.155 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.9
DANN	Benign	0.52
PhyloP100		0.082
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs497239; hg19: chr6-31908761;