chr5-40985502-C-T

Variant names:

• chr5-40985502-C-T
• rs4957361
• ENST00000706664.1:n.2464+5593C>T

Variant summary

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

The ENST00000706664.1(C7):​n.2464+5593C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,036 control chromosomes in the GnomAD database, including 16,691 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 0.46 (16691 hom., cov: 33)
• Consequence: C7 ENST00000706664.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 8 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 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+5593C>T		intron	N/A
	C7	ENST00000706666.1		n.2241+8662C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69341 AN: 151918 Hom.: 16663 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.457 AC: 69414 AN: 152036 Hom.: 16691 Cov.: 33 AF XY: 0.459 AC XY: 34071 AN XY: 74308

African (AFR) AF: 0.612 AC: 25361 AN: 41472

American (AMR) AF: 0.458 AC: 6993 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1555 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2572 AN: 5170

South Asian (SAS) AF: 0.529 AC: 2552 AN: 4824

European-Finnish (FIN) AF: 0.359 AC: 3793 AN: 10562

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25202 AN: 67964

Other (OTH) AF: 0.437 AC: 922 AN: 2110

Alfa AF: 0.402 Hom.: 54285

Bravo AF: 0.470

Asia WGS AF: 0.529 AC: 1843 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.80
PhyloP100		-0.70

Splicing

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

Other links and lift over

dbSNP: rs4957361; hg19: chr5-40985604;