5-40985982-T-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000706664.1	n.2464+6073T>G		intron_variant	Intron 17 of 18
C7	ENST00000706666.1	n.2241+9142T>G		intron_variant	Intron 16 of 16

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

Gnomad4 AFR AF: 0.0691

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.289

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.223

Alfa AF: 0.210 Hom.: 1789

Bravo AF: 0.175

Asia WGS AF: 0.309 AC: 1071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13161930; hg19: chr5-40986084;