rs8264

Positions:

• chr5-40982678-A-G

Variant summary

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

The NM_000587.4(C7):​c.*1105A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,262 control chromosomes in the GnomAD database, including 2,567 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 0.18 (2565 hom., cov: 33)
  • Exomes 𝑓: 0.13 (2 hom.)
• Consequence: C7 NM_000587.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

Genes affected

C7 (HGNC:1346): (complement C7) This gene encodes a serum glycoprotein that forms a membrane attack complex together with complement components C5b, C6, C8, and C9 as part of the terminal complement pathway of the innate immune system. The protein encoded by this gene contains a cholesterol-dependent cytolysin/membrane attack complex/perforin-like (CDC/MACPF) domain and belongs to a large family of structurally related molecules that form pores involved in host immunity and bacterial pathogenesis. This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. Mutations in this gene are associated with a rare disorder called C7 deficiency. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7	NM_000587.4	c.*1105A>G		3_prime_UTR_variant	18/18	ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10	c.*1105A>G		3_prime_UTR_variant	18/18	1	NM_000587.4	ENSP00000322061	P1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27232 AN: 152006 Hom.: 2567 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.130 AC: 18 AN: 138 Hom.: 2 Cov.: 0 AF XY: 0.171 AC XY: 13 AN XY: 76

Gnomad4 EAS exome AF: 0.132

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.179 AC: 27233 AN: 152124 Hom.: 2565 Cov.: 33 AF XY: 0.175 AC XY: 13028 AN XY: 74368

Gnomad4 AFR AF: 0.245

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.169

Alfa AF: 0.165 Hom.: 2899

Bravo AF: 0.182

Asia WGS AF: 0.0990 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs8264; hg19: chr5-40982780;