Variant rs3745567 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000064.4(C3):c.3391-33G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,539,970 control chromosomes in the GnomAD database, including 11,704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.11 ( 1027 hom., cov: 33)

Exomes 𝑓: 0.12 ( 10677 hom. )

Consequence

C3
NM_000064.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.429

Variant links:

Genes affected

C3 (HGNC:1318): (complement C3) Complement component C3 plays a central role in the activation of complement system. Its activation is required for both classical and alternative complement activation pathways. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that form the mature protein, which is then further processed to generate numerous peptide products. The C3a peptide, also known as the C3a anaphylatoxin, modulates inflammation and possesses antimicrobial activity. Mutations in this gene are associated with atypical hemolytic uremic syndrome and age-related macular degeneration in human patients. [provided by RefSeq, Nov 2015]

C3 links:

C3 (HGNC:):

C3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 19-6690760-C-T is Benign according to our data. Variant chr19-6690760-C-T is described in ClinVar as [Benign]. Clinvar id is 1226583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C3	NM_000064.4 linkuse as main transcript	c.3391-33G>A		intron_variant		ENST00000245907.11	NP_000055.2	P01024V9HWA9B4DR57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C3	ENST00000245907.11 linkuse as main transcript	c.3391-33G>A		intron_variant		1	NM_000064.4	ENSP00000245907.4		P01024

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16075

AN:

152190

Hom.:

1026

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0559

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.100

Gnomad ASJ

AF:

0.182

Gnomad EAS

AF:

0.0761

Gnomad SAS

AF:

0.0788

Gnomad FIN

AF:

0.177

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.119

GnomAD3 exomes

AF:

0.112

AC:

27336

AN:

244086

Hom.:

1654

AF XY:

0.114

AC XY:

15096

AN XY:

132022

show subpopulations

Gnomad AFR exome

AF:

0.0537

Gnomad AMR exome

AF:

0.0749

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.0762

Gnomad SAS exome

AF:

0.0799

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.121

AC:

167383

AN:

1387660

Hom.:

10677

Cov.:

AF XY:

0.120

AC XY:

83259

AN XY:

694008

show subpopulations

Gnomad4 AFR exome

AF:

0.0519

Gnomad4 AMR exome

AF:

0.0799

Gnomad4 ASJ exome

AF:

0.179

Gnomad4 EAS exome

AF:

0.0706

Gnomad4 SAS exome

AF:

0.0801

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.126

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.106

AC:

16085

AN:

152310

Hom.:

1027

Cov.:

AF XY:

0.106

AC XY:

7928

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0559

Gnomad4 AMR

AF:

0.0999

Gnomad4 ASJ

AF:

0.182

Gnomad4 EAS

AF:

0.0757

Gnomad4 SAS

AF:

0.0795

Gnomad4 FIN

AF:

0.177

Gnomad4 NFE

AF:

0.126

Gnomad4 OTH

AF:

0.120

Alfa

AF:

0.120

Hom.:

1244

Bravo

AF:

0.0991

Asia WGS

AF:

0.0800

AC:

279

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.91

BranchPoint Hunter

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over