chr5-40939189-A-G

Variant names:

• chr5-40939189-A-G
• rs2455314
• NM_000587.4:c.567+1499A>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.567+1499A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,100 control chromosomes in the GnomAD database, including 16,121 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 0.45 (16121 hom., cov: 33)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 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.567+1499A>G		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.567+1499A>G		intron	N/A	ENSP00000322061.9
	C7	ENST00000696333.1		c.567+1499A>G		intron	N/A	ENSP00000512566.1
	C7	ENST00000696441.1		c.567+1499A>G		intron	N/A	ENSP00000512631.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68864 AN: 151982 Hom.: 16106 Cov.: 33

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.453 AC: 68918 AN: 152100 Hom.: 16121 Cov.: 33 AF XY: 0.450 AC XY: 33476 AN XY: 74354

African (AFR) AF: 0.589 AC: 24413 AN: 41450

American (AMR) AF: 0.423 AC: 6465 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3472

East Asian (EAS) AF: 0.371 AC: 1923 AN: 5184

South Asian (SAS) AF: 0.457 AC: 2206 AN: 4830

European-Finnish (FIN) AF: 0.382 AC: 4049 AN: 10588

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.401 AC: 27230 AN: 67982

Other (OTH) AF: 0.433 AC: 915 AN: 2112

Alfa AF: 0.416 Hom.: 7624

Bravo AF: 0.463

Asia WGS AF: 0.456 AC: 1585 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.80
PhyloP100		0.0010
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: rs2455314; hg19: chr5-40939291;