5-40987272-T-C

Variant names:

• chr5-40987272-T-C
• rs2122564
• ENST00000706664.1:n.2464+7363T>C

Variant summary

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

The ENST00000706664.1(C7):​n.2464+7363T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 152,048 control chromosomes in the GnomAD database, including 25,161 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 0.57 (25161 hom., cov: 32)
• Consequence: C7 ENST00000706664.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	ENST00000706664.1		n.2464+7363T>C		intron	N/A
	C7	ENST00000706666.1		n.2241+10432T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86441 AN: 151930 Hom.: 25126 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.569 AC: 86533 AN: 152048 Hom.: 25161 Cov.: 32 AF XY: 0.576 AC XY: 42784 AN XY: 74310

African (AFR) AF: 0.485 AC: 20091 AN: 41458

American (AMR) AF: 0.597 AC: 9117 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2447 AN: 3470

East Asian (EAS) AF: 0.838 AC: 4343 AN: 5184

South Asian (SAS) AF: 0.800 AC: 3860 AN: 4828

European-Finnish (FIN) AF: 0.544 AC: 5741 AN: 10552

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38942 AN: 67974

Other (OTH) AF: 0.596 AC: 1257 AN: 2108

Alfa AF: 0.579 Hom.: 30498

Bravo AF: 0.566

Asia WGS AF: 0.814 AC: 2830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.75
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs2122564; hg19: chr5-40987374;