5-40961062-A-G

Variant names:

• chr5-40961062-A-G
• rs1901167
• NM_000587.4:c.1662-1023A>G

Variant summary

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

The NM_000587.4(C7):​c.1662-1023A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,044 control chromosomes in the GnomAD database, including 5,865 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 0.27 (5865 hom., cov: 32)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C7	NM_000587.4	c.1662-1023A>G		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.1662-1023A>G		intron_variant	Intron 12 of 17	1	NM_000587.4	ENSP00000322061.9

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41148 AN: 151926 Hom.: 5858 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.271 AC: 41187 AN: 152044 Hom.: 5865 Cov.: 32 AF XY: 0.275 AC XY: 20444 AN XY: 74342

African (AFR) AF: 0.345 AC: 14299 AN: 41422

American (AMR) AF: 0.194 AC: 2959 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1003 AN: 3472

East Asian (EAS) AF: 0.377 AC: 1948 AN: 5162

South Asian (SAS) AF: 0.352 AC: 1698 AN: 4822

European-Finnish (FIN) AF: 0.253 AC: 2671 AN: 10578

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15722 AN: 67982

Other (OTH) AF: 0.272 AC: 576 AN: 2114

Alfa AF: 0.246 Hom.: 20517

Bravo AF: 0.267

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.97
DANN	Benign	0.56
PhyloP100		-0.26
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: rs1901167; hg19: chr5-40961164;