5-40985982-T-G

Variant names:

• chr5-40985982-T-G
• rs13161930
• ENST00000706664.1:n.2464+6073T>G

Variant summary

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

The ENST00000706664.1(C7):​n.2464+6073T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,204 control chromosomes in the GnomAD database, including 3,266 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 0.19 (3266 hom., cov: 33)
• Consequence: C7 ENST00000706664.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.208
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	ENST00000706664.1		n.2464+6073T>G		intron	N/A
	C7	ENST00000706666.1		n.2241+9142T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28834 AN: 152086 Hom.: 3265 Cov.: 33

Gnomad AFR AF: 0.0690

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.190 AC: 28846 AN: 152204 Hom.: 3266 Cov.: 33 AF XY: 0.196 AC XY: 14572 AN XY: 74394

African (AFR) AF: 0.0691 AC: 2871 AN: 41556

American (AMR) AF: 0.175 AC: 2672 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3470

East Asian (EAS) AF: 0.296 AC: 1533 AN: 5176

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4822

European-Finnish (FIN) AF: 0.250 AC: 2639 AN: 10576

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15724 AN: 67996

Other (OTH) AF: 0.223 AC: 470 AN: 2112

Alfa AF: 0.212 Hom.: 2030

Bravo AF: 0.175

Asia WGS AF: 0.309 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs13161930; hg19: chr5-40986084;