NM_000587.4:c.*1105A>G

Variant names:

• chr5-40982678-A-G
• rs8264
• NM_000587.4:c.*1105A>G

Variant summary

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

The NM_000587.4(C7):​c.*1105A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,262 control chromosomes in the GnomAD database, including 2,567 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 0.18 (2565 hom., cov: 33)
  • Exomes 𝑓: 0.13 (2 hom.)
• Consequence: C7 NM_000587.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 10 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000587.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	NM_000587.4	MANE Select	c.*1105A>G		3_prime_UTR	Exon 18 of 18	NP_000578.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C7	ENST00000313164.10	TSL:1 MANE Select	c.*1105A>G		3_prime_UTR	Exon 18 of 18	ENSP00000322061.9
	C7	ENST00000908410.1		c.*1105A>G		3_prime_UTR	Exon 19 of 19	ENSP00000578469.1
	C7	ENST00000908412.1		c.*1105A>G		3_prime_UTR	Exon 19 of 19	ENSP00000578471.1

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27232 AN: 152006 Hom.: 2567 Cov.: 33

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0685

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.130 AC: 18 AN: 138 Hom.: 2 Cov.: 0 AF XY: 0.171 AC XY: 13 AN XY: 76

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.132 AC: 18 AN: 136

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.179 AC: 27233 AN: 152124 Hom.: 2565 Cov.: 33 AF XY: 0.175 AC XY: 13028 AN XY: 74368

African (AFR) AF: 0.245 AC: 10152 AN: 41484

American (AMR) AF: 0.134 AC: 2047 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3470

East Asian (EAS) AF: 0.0692 AC: 358 AN: 5170

South Asian (SAS) AF: 0.107 AC: 517 AN: 4828

European-Finnish (FIN) AF: 0.180 AC: 1907 AN: 10584

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11191 AN: 67988

Other (OTH) AF: 0.169 AC: 357 AN: 2110

Alfa AF: 0.168 Hom.: 3817

Bravo AF: 0.182

Asia WGS AF: 0.0990 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.2
DANN	Benign	0.47
PhyloP100		0.14
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: rs8264; hg19: chr5-40982780;