chr5-40991242-C-T

Variant names:

• chr5-40991242-C-T
• rs7736582
• ENST00000706664.1:n.2464+11333C>T

Variant summary

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

The ENST00000706664.1(C7):​n.2464+11333C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 152,142 control chromosomes in the GnomAD database, including 61,971 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 0.90 (61971 hom., cov: 32)
• Consequence: C7 ENST00000706664.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.905 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+11333C>T		intron	N/A
	C7	ENST00000706666.1		n.2241+14402C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.902 AC: 137135 AN: 152024 Hom.: 61914 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.878

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.927

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.905

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.902 AC: 137253 AN: 152142 Hom.: 61971 Cov.: 32 AF XY: 0.902 AC XY: 67083 AN XY: 74368

African (AFR) AF: 0.909 AC: 37718 AN: 41492

American (AMR) AF: 0.869 AC: 13270 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 3045 AN: 3470

East Asian (EAS) AF: 0.866 AC: 4467 AN: 5160

South Asian (SAS) AF: 0.927 AC: 4476 AN: 4826

European-Finnish (FIN) AF: 0.935 AC: 9892 AN: 10582

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.905 AC: 61593 AN: 68022

Other (OTH) AF: 0.871 AC: 1837 AN: 2108

Alfa AF: 0.900 Hom.: 132473

Bravo AF: 0.896

Asia WGS AF: 0.907 AC: 3153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0060
DANN	Benign	0.39
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs7736582; hg19: chr5-40991344;