rs2271709

Positions:

• chr5-40931255-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.138+116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 728,586 control chromosomes in the GnomAD database, including 18,466 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 0.26 (5792 hom., cov: 33)
  • Exomes 𝑓: 0.20 (12674 hom.)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.749

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]

C7 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7	NM_000587.4	c.138+116A>G		intron_variant		ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10	c.138+116A>G		intron_variant		1	NM_000587.4	ENSP00000322061.9

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38931 AN: 152036 Hom.: 5786 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.202 AC: 116657 AN: 576432 Hom.: 12674 AF XY: 0.202 AC XY: 61234 AN XY: 302692

Gnomad4 AFR exome AF: 0.421

Gnomad4 AMR exome AF: 0.184

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.214

GnomAD4 genome AF: 0.256 AC: 38961 AN: 152154 Hom.: 5792 Cov.: 33 AF XY: 0.253 AC XY: 18804 AN XY: 74408

Gnomad4 AFR AF: 0.422

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.183

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.190

Gnomad4 OTH AF: 0.253

Alfa AF: 0.205 Hom.: 1583

Bravo AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.46

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: rs2271709; hg19: chr5-40931357;