rs10512751

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000587.4(C7):​c.280+264A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,182 control chromosomes in the GnomAD database, including 1,465 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 0.13 ( 1465 hom., cov: 32)

Consequence

C7
NM_000587.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.355
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
C7NM_000587.4 linkuse as main transcriptc.280+264A>C intron_variant ENST00000313164.10 NP_000578.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
C7ENST00000313164.10 linkuse as main transcriptc.280+264A>C intron_variant 1 NM_000587.4 ENSP00000322061 P1

Frequencies

GnomAD3 genomes
AF:
0.126
AC:
19199
AN:
152064
Hom.:
1462
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0326
Gnomad AMI
AF:
0.186
Gnomad AMR
AF:
0.157
Gnomad ASJ
AF:
0.175
Gnomad EAS
AF:
0.142
Gnomad SAS
AF:
0.160
Gnomad FIN
AF:
0.117
Gnomad MID
AF:
0.149
Gnomad NFE
AF:
0.170
Gnomad OTH
AF:
0.157
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.126
AC:
19209
AN:
152182
Hom.:
1465
Cov.:
32
AF XY:
0.125
AC XY:
9302
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0326
Gnomad4 AMR
AF:
0.156
Gnomad4 ASJ
AF:
0.175
Gnomad4 EAS
AF:
0.142
Gnomad4 SAS
AF:
0.163
Gnomad4 FIN
AF:
0.117
Gnomad4 NFE
AF:
0.170
Gnomad4 OTH
AF:
0.155
Alfa
AF:
0.164
Hom.:
2342
Bravo
AF:
0.126
Asia WGS
AF:
0.142
AC:
493
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
0.92
DANN
Benign
0.45

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs10512751; hg19: chr5-40934832; API