chr1-56912477-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000562.3(C8A):​c.1455C>T​(p.Arg485=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0623 in 1,614,082 control chromosomes in the GnomAD database, including 4,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1237 hom., cov: 33)
Exomes 𝑓: 0.058 ( 3542 hom. )

Consequence

C8A
NM_000562.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0140
Variant links:
Genes affected
C8A (HGNC:1352): (complement C8 alpha chain) C8 is a component of the complement system and contains three polypeptides, alpha, beta and gamma. This gene encodes the alpha subunit of C8. C8 participates in the formation of the membrane attack complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause complement C8 alpha-gamma deficiency. [provided by RefSeq, Nov 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.68).
BP6
Variant 1-56912477-C-T is Benign according to our data. Variant chr1-56912477-C-T is described in ClinVar as [Benign]. Clinvar id is 402462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.014 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C8ANM_000562.3 linkuse as main transcriptc.1455C>T p.Arg485= synonymous_variant 10/11 ENST00000361249.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C8AENST00000361249.4 linkuse as main transcriptc.1455C>T p.Arg485= synonymous_variant 10/111 NM_000562.3 P4

Frequencies

GnomAD3 genomes
AF:
0.102
AC:
15577
AN:
152120
Hom.:
1235
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.216
Gnomad AMI
AF:
0.0482
Gnomad AMR
AF:
0.108
Gnomad ASJ
AF:
0.0415
Gnomad EAS
AF:
0.0517
Gnomad SAS
AF:
0.138
Gnomad FIN
AF:
0.0470
Gnomad MID
AF:
0.117
Gnomad NFE
AF:
0.0459
Gnomad OTH
AF:
0.104
GnomAD3 exomes
AF:
0.0756
AC:
19007
AN:
251306
Hom.:
1071
AF XY:
0.0752
AC XY:
10218
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.225
Gnomad AMR exome
AF:
0.0917
Gnomad ASJ exome
AF:
0.0454
Gnomad EAS exome
AF:
0.0518
Gnomad SAS exome
AF:
0.134
Gnomad FIN exome
AF:
0.0483
Gnomad NFE exome
AF:
0.0456
Gnomad OTH exome
AF:
0.0711
GnomAD4 exome
AF:
0.0581
AC:
84892
AN:
1461844
Hom.:
3542
Cov.:
33
AF XY:
0.0598
AC XY:
43481
AN XY:
727226
show subpopulations
Gnomad4 AFR exome
AF:
0.228
Gnomad4 AMR exome
AF:
0.0928
Gnomad4 ASJ exome
AF:
0.0431
Gnomad4 EAS exome
AF:
0.0650
Gnomad4 SAS exome
AF:
0.132
Gnomad4 FIN exome
AF:
0.0459
Gnomad4 NFE exome
AF:
0.0457
Gnomad4 OTH exome
AF:
0.0681
GnomAD4 genome
AF:
0.102
AC:
15599
AN:
152238
Hom.:
1237
Cov.:
33
AF XY:
0.102
AC XY:
7597
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.216
Gnomad4 AMR
AF:
0.108
Gnomad4 ASJ
AF:
0.0415
Gnomad4 EAS
AF:
0.0517
Gnomad4 SAS
AF:
0.139
Gnomad4 FIN
AF:
0.0470
Gnomad4 NFE
AF:
0.0459
Gnomad4 OTH
AF:
0.102
Alfa
AF:
0.0665
Hom.:
286
Bravo
AF:
0.110
Asia WGS
AF:
0.107
AC:
374
AN:
3478
EpiCase
AF:
0.0480
EpiControl
AF:
0.0511

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 05, 2024- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 28, 2016Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.68
CADD
Benign
3.5
DANN
Benign
0.40

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: rs1620073; hg19: chr1-57378150; COSMIC: COSV63484443; API