chr5-40987272-T-C

Position:

• chr5-40987272-T-C

Variant summary

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

The ENST00000706664.1(C7):​n.2464+7363T>C 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 0.569 in 152,048 control chromosomes in the GnomAD database, including 25,161 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 0.57 (25161 hom., cov: 32)
• Consequence: C7 ENST00000706664.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 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+7363T>C		intron_variant, non_coding_transcript_variant
C7	ENST00000706666.1	n.2241+10432T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.569 AC: 86441 AN: 151930 Hom.: 25126 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.569 AC: 86533 AN: 152048 Hom.: 25161 Cov.: 32 AF XY: 0.576 AC XY: 42784 AN XY: 74310

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.596

Alfa AF: 0.583 Hom.: 23237

Bravo AF: 0.566

Asia WGS AF: 0.814 AC: 2830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2122564; hg19: chr5-40987374;