chr5-40961792-C-A

Variant names:

• chr5-40961792-C-A
• rs324058
• NM_000587.4:c.1662-293C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000587.4(C7):​c.1662-293C>A 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 152,148 control chromosomes in the GnomAD database, including 46,266 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 (46266 hom., cov: 32)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 8 publications found

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]

C7 Gene-Disease associations (from GenCC):

• complement component 7 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• 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 rank	MANE	Protein	UniProt
C7	NM_000587.4	c.1662-293C>A		intron_variant	Intron 12 of 17	ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10	c.1662-293C>A		intron_variant	Intron 12 of 17	1	NM_000587.4	ENSP00000322061.9

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118465 AN: 152030 Hom.: 46225 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.927

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: 118566 AN: 152148 Hom.: 46266 Cov.: 32 AF XY: 0.785 AC XY: 58383 AN XY: 74390

African (AFR) AF: 0.811 AC: 33640 AN: 41484

American (AMR) AF: 0.738 AC: 11273 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2966 AN: 3472

East Asian (EAS) AF: 0.925 AC: 4805 AN: 5192

South Asian (SAS) AF: 0.927 AC: 4479 AN: 4830

European-Finnish (FIN) AF: 0.767 AC: 8128 AN: 10592

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50638 AN: 67986

Other (OTH) AF: 0.784 AC: 1652 AN: 2108

Alfa AF: 0.763 Hom.: 74347

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	-0.95
CADD	Benign	3.5
DANN	Benign	0.43
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs324058; hg19: chr5-40961894;