chr5-40983334-G-A

Position:

• chr5-40983334-G-A

Variant summary

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

The NM_000587.4(C7):​c.*1761G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 151,976 control chromosomes in the GnomAD database, including 2,971 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 0.19 (2971 hom., cov: 32)
• Consequence: C7 NM_000587.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C7	NM_000587.4	c.*1761G>A		3_prime_UTR_variant	18/18	ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10	c.*1761G>A		3_prime_UTR_variant	18/18	1	NM_000587.4	ENSP00000322061	P1
C7	ENST00000706664.1	n.2464+3425G>A		intron_variant, non_coding_transcript_variant
C7	ENST00000706666.1	n.2241+6494G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28739 AN: 151858 Hom.: 2967 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0667

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.189 AC: 28761 AN: 151976 Hom.: 2971 Cov.: 32 AF XY: 0.185 AC XY: 13735 AN XY: 74282

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0675

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.179

Alfa AF: 0.201 Hom.: 455

Bravo AF: 0.193

Asia WGS AF: 0.102 AC: 356 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7732104; hg19: chr5-40983436;