5-40976233-G-T

Position:

• chr5-40976233-G-T

Variant summary

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

The NM_000587.4(C7):​c.2075-517G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 152,242 control chromosomes in the GnomAD database, including 863 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 (863 hom., cov: 33)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C7	NM_000587.4	c.2075-517G>T		intron_variant		ENST00000313164.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C7	ENST00000313164.10	c.2075-517G>T		intron_variant		1	NM_000587.4	P1

Frequencies

GnomAD3 genomes AF: 0.0908 AC: 13807 AN: 152124 Hom.: 863 Cov.: 33

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.0882

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0907 AC: 13804 AN: 152242 Hom.: 863 Cov.: 33 AF XY: 0.0921 AC XY: 6853 AN XY: 74438

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.0804

Gnomad4 FIN AF: 0.0882

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0577 Hom.: 74

Bravo AF: 0.0958

Asia WGS AF: 0.113 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.2
DANN	Benign	0.63

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: rs3828511; hg19: chr5-40976335;