NM_000587.4:c.62+659G>C

Variant names:

• chr5-40929294-G-C
• rs3792633
• NM_000587.4:c.62+659G>C

Variant summary

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

The NM_000587.4(C7):​c.62+659G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,194 control chromosomes in the GnomAD database, including 1,309 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 0.12 (1309 hom., cov: 32)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000587.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	NM_000587.4	MANE Select	c.62+659G>C		intron	N/A	NP_000578.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	ENST00000313164.10	TSL:1 MANE Select	c.62+659G>C		intron	N/A	ENSP00000322061.9
	C7	ENST00000706665.1		n.834G>C		non_coding_transcript_exon	Exon 2 of 2
	C7	ENST00000696333.1		c.62+659G>C		intron	N/A	ENSP00000512566.1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18546 AN: 152076 Hom.: 1306 Cov.: 32

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.122 AC: 18560 AN: 152194 Hom.: 1309 Cov.: 32 AF XY: 0.122 AC XY: 9081 AN XY: 74402

African (AFR) AF: 0.0493 AC: 2049 AN: 41536

American (AMR) AF: 0.152 AC: 2323 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 592 AN: 3468

East Asian (EAS) AF: 0.143 AC: 739 AN: 5172

South Asian (SAS) AF: 0.159 AC: 768 AN: 4818

European-Finnish (FIN) AF: 0.112 AC: 1189 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10372 AN: 68006

Other (OTH) AF: 0.150 AC: 317 AN: 2116

Alfa AF: 0.0552 Hom.: 65

Bravo AF: 0.123

Asia WGS AF: 0.141 AC: 488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.48
PhyloP100		0.069
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: rs3792633; hg19: chr5-40929396;