rs2876849

Positions:

• chr5-40979688-A-T

Variant summary

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

The NM_000587.4(C7):​c.2166-37A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,563,806 control chromosomes in the GnomAD database, including 37,556 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 (2967 hom., cov: 31)
  • Exomes 𝑓: 0.22 (34589 hom.)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C7	NM_000587.4	c.2166-37A>T		intron_variant		ENST00000313164.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C7	ENST00000313164.10	c.2166-37A>T		intron_variant		1	NM_000587.4	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27348 AN: 151848 Hom.: 2966 Cov.: 31

Gnomad AFR AF: 0.0661

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.223 AC: 51723 AN: 232424 Hom.: 6292 AF XY: 0.233 AC XY: 29394 AN XY: 126090

Gnomad AFR exome AF: 0.0642

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.307

Gnomad SAS exome AF: 0.316

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.225

GnomAD4 exome AF: 0.215 AC: 303666 AN: 1411840 Hom.: 34589 Cov.: 23 AF XY: 0.220 AC XY: 153397 AN XY: 698484

Gnomad4 AFR exome AF: 0.0631

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.269

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.239

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.180 AC: 27357 AN: 151966 Hom.: 2967 Cov.: 31 AF XY: 0.187 AC XY: 13868 AN XY: 74282

Gnomad4 AFR AF: 0.0661

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.208

Alfa AF: 0.213 Hom.: 729

Bravo AF: 0.166

Asia WGS AF: 0.305 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.6
DANN	Benign	0.76

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: rs2876849; hg19: chr5-40979790;