5-40987997-G-A

Position:

• chr5-40987997-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000706664.1(C7):​n.2464+8088G>A variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0980

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000706664.1	n.2464+8088G>A		intron_variant, non_coding_transcript_variant
C7	ENST00000706666.1	n.2241+11157G>A		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0932

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.264

Gnomad4 FIN AF: 0.146

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.173

Alfa AF: 0.158 Hom.: 386

Bravo AF: 0.147

Asia WGS AF: 0.280 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1376174; hg19: chr5-40988099;