rs324057

chr5-40961678-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.1662-407A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 152,122 control chromosomes in the GnomAD database, including 46,235 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 0.78 (46235 hom., cov: 31)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.76

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=-1.05).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C7	NM_000587.4	c.1662-407A>G		intron_variant		ENST00000313164.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C7	ENST00000313164.10	c.1662-407A>G		intron_variant		1	NM_000587.4	P1

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118411 AN: 152002 Hom.: 46193 Cov.: 31

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.928

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.781

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.779 AC: 118514 AN: 152122 Hom.: 46235 Cov.: 31 AF XY: 0.785 AC XY: 58339 AN XY: 74356

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.738

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.928

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.745

Gnomad4 OTH AF: 0.784

Alfa AF: 0.772 Hom.: 5630

Bravo AF: 0.778

Asia WGS AF: 0.926 AC: 3221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
Cadd	Benign	0.027
Dann	Benign	0.097

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: rs324057; hg19: chr5-40961780; COSMIC: COSV57481755; COSMIC: COSV57481755;