rs7713884

chr5-40964714-C-Achr5-40964714-C-G

Variant summary

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

The NM_000587.4(C7):c.1750-27C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,599,236 control chromosomes in the GnomAD database, including 46,542 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 0.27 (5590 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40952 hom.)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C7	NM_000587.4	c.1750-27C>A		intron_variant		ENST00000313164.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C7	ENST00000313164.10	c.1750-27C>A		intron_variant		1	NM_000587.4	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40272 AN: 151870 Hom.: 5588 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.263

GnomAD3 exomes AF: 0.250 AC: 61274 AN: 245016 Hom.: 8237 AF XY: 0.256 AC XY: 33983 AN XY: 132756

Gnomad AFR exome AF: 0.346

Gnomad AMR exome AF: 0.161

Gnomad ASJ exome AF: 0.281

Gnomad EAS exome AF: 0.349

Gnomad SAS exome AF: 0.327

Gnomad FIN exome AF: 0.232

Gnomad NFE exome AF: 0.229

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.233 AC: 336539 AN: 1447248 Hom.: 40952 Cov.: 28 AF XY: 0.236 AC XY: 170046 AN XY: 720216

Gnomad4 AFR exome AF: 0.349

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.280

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.265 AC: 40304 AN: 151988 Hom.: 5590 Cov.: 32 AF XY: 0.269 AC XY: 19942 AN XY: 74272

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.335

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.268

Alfa AF: 0.252 Hom.: 908

Bravo AF: 0.262

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	3.8
Dann	Benign	0.59

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: rs7713884; hg19: chr5-40964816; COSMIC: COSV57480693; COSMIC: COSV57480693;