chr5-40934730-A-C

Variant names:

• chr5-40934730-A-C
• rs10512751
• NM_000587.4:c.280+264A>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.280+264A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,182 control chromosomes in the GnomAD database, including 1,465 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 0.13 (1465 hom., cov: 32)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C7	NM_000587.4	c.280+264A>C		intron_variant	Intron 4 of 17	ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10	c.280+264A>C		intron_variant	Intron 4 of 17	1	NM_000587.4	ENSP00000322061.9

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19199 AN: 152064 Hom.: 1462 Cov.: 32

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.157

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

GnomAD4 genome AF: 0.126 AC: 19209 AN: 152182 Hom.: 1465 Cov.: 32 AF XY: 0.125 AC XY: 9302 AN XY: 74412

African (AFR) AF: 0.0326 AC: 1353 AN: 41554

American (AMR) AF: 0.156 AC: 2390 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 605 AN: 3460

East Asian (EAS) AF: 0.142 AC: 733 AN: 5162

South Asian (SAS) AF: 0.163 AC: 785 AN: 4824

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10604

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11564 AN: 67982

Other (OTH) AF: 0.155 AC: 329 AN: 2116

Alfa AF: 0.159 Hom.: 2867

Bravo AF: 0.126

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.92
DANN	Benign	0.45
PhyloP100		-0.35
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: rs10512751; hg19: chr5-40934832;