chr5-40987997-G-A

Variant names:

• chr5-40987997-G-A
• rs1376174
• ENST00000706664.1:n.2464+8088G>A

Variant summary

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

The ENST00000706664.1(C7):​n.2464+8088G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,162 control chromosomes in the GnomAD database, including 1,969 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 0.15 (1969 hom., cov: 32)
• Consequence: C7 ENST00000706664.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980
• Publications: 2 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 = 0.257 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000706664.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	ENST00000706664.1		n.2464+8088G>A		intron	N/A
	C7	ENST00000706666.1		n.2241+11157G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23292 AN: 152044 Hom.: 1966 Cov.: 32

Gnomad AFR AF: 0.0931

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.153 AC: 23306 AN: 152162 Hom.: 1969 Cov.: 32 AF XY: 0.155 AC XY: 11560 AN XY: 74386

African (AFR) AF: 0.0932 AC: 3871 AN: 41524

American (AMR) AF: 0.132 AC: 2013 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 861 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1389 AN: 5176

South Asian (SAS) AF: 0.264 AC: 1271 AN: 4816

European-Finnish (FIN) AF: 0.146 AC: 1543 AN: 10578

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.173 AC: 11785 AN: 67994

Other (OTH) AF: 0.173 AC: 365 AN: 2114

Alfa AF: 0.168 Hom.: 834

Bravo AF: 0.147

Asia WGS AF: 0.280 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.58
PhyloP100		-0.098

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1376174; hg19: chr5-40988099;