rs3805226

Variant names:

• chr5-40973903-A-G
• rs3805226
• NM_000587.4:c.2074+1309A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-40973903-A-G
• chr5-40973903-A-T

Variant summary

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

The NM_000587.4(C7):​c.2074+1309A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 152,232 control chromosomes in the GnomAD database, including 869 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 0.091 (869 hom., cov: 33)
• Consequence: C7 NM_000587.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 7 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=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C7	NM_000587.4	c.2074+1309A>G		intron_variant	Intron 15 of 17	ENST00000313164.10	NP_000578.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10	c.2074+1309A>G		intron_variant	Intron 15 of 17	1	NM_000587.4	ENSP00000322061.9

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 13862 AN: 152114 Hom.: 869 Cov.: 33

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0795

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.0910 AC: 13859 AN: 152232 Hom.: 869 Cov.: 33 AF XY: 0.0924 AC XY: 6874 AN XY: 74430

African (AFR) AF: 0.0290 AC: 1205 AN: 41570

American (AMR) AF: 0.144 AC: 2202 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3470

East Asian (EAS) AF: 0.187 AC: 966 AN: 5178

South Asian (SAS) AF: 0.0802 AC: 387 AN: 4824

European-Finnish (FIN) AF: 0.0884 AC: 936 AN: 10590

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 7001 AN: 68004

Other (OTH) AF: 0.112 AC: 237 AN: 2116

Alfa AF: 0.102 Hom.: 2504

Bravo AF: 0.0961

Asia WGS AF: 0.114 AC: 399 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.1
DANN	Benign	0.85
PhyloP100		0.025
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3805226; hg19: chr5-40974005;