rs1055021

Positions:

• chr5-40980064-C-A
• chr5-40980064-C-T

Variant summary

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

The ENST00000313164.10(C7):​c.2350+155C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 516,112 control chromosomes in the GnomAD database, including 3,602 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 0.091 (873 hom., cov: 32)
  • Exomes 𝑓: 0.12 (2729 hom.)
• Consequence: C7 ENST00000313164.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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 (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7	NM_000587.4	c.2350+155C>A		intron_variant		ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10	c.2350+155C>A		intron_variant		1	NM_000587.4	ENSP00000322061	P1

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13867 AN: 152100 Hom.: 873 Cov.: 32

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0799

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.116 AC: 42348 AN: 363894 Hom.: 2729 Cov.: 5 AF XY: 0.116 AC XY: 21459 AN XY: 185228

Gnomad4 AFR exome AF: 0.0311

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.225

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.0904

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.117

GnomAD4 genome AF: 0.0911 AC: 13864 AN: 152218 Hom.: 873 Cov.: 32 AF XY: 0.0927 AC XY: 6896 AN XY: 74430

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0406 Hom.: 44

Bravo AF: 0.0962

Asia WGS AF: 0.114 AC: 398 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	2.9
DANN	Benign	0.68

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: rs1055021; hg19: chr5-40980166;