Variant 19-6679349-T-C 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.4546+58A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.776 in 1,484,326 control chromosomes in the GnomAD database, including 449,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 48732 hom., cov: 31)

Exomes 𝑓: 0.77 ( 400362 hom. )

Consequence

C3
NM_000064.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.581

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 19-6679349-T-C is Benign according to our data. Variant chr19-6679349-T-C is described in ClinVar as [Benign]. Clinvar id is 1192668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3	NM_000064.4 linkuse as main transcript	c.4546+58A>G		intron_variant		ENST00000245907.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3	ENST00000245907.11 linkuse as main transcript	c.4546+58A>G		intron_variant		1	NM_000064.4	P1

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

121167

AN:

151956

Hom.:

48680

Cov.:

show subpopulations

Gnomad AFR

AF:

0.891

Gnomad AMI

AF:

0.724

Gnomad AMR

AF:

0.744

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.829

Gnomad FIN

AF:

0.725

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.776

Gnomad OTH

AF:

0.798

GnomAD4 exome

AF:

0.774

AC:

1030735

AN:

1332252

Hom.:

400362

Cov.:

AF XY:

0.776

AC XY:

519644

AN XY:

669914

show subpopulations

Gnomad4 AFR exome

AF:

0.899

Gnomad4 AMR exome

AF:

0.702

Gnomad4 ASJ exome

AF:

0.683

Gnomad4 EAS exome

AF:

0.668

Gnomad4 SAS exome

AF:

0.831

Gnomad4 FIN exome

AF:

0.749

Gnomad4 NFE exome

AF:

0.776

Gnomad4 OTH exome

AF:

0.771

GnomAD4 genome

AF:

0.797

AC:

121276

AN:

152074

Hom.:

48732

Cov.:

AF XY:

0.792

AC XY:

58888

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.891

Gnomad4 AMR

AF:

0.743

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.702

Gnomad4 SAS

AF:

0.828

Gnomad4 FIN

AF:

0.725

Gnomad4 NFE

AF:

0.776

Gnomad4 OTH

AF:

0.799

Alfa

AF:

0.775

Hom.:

43055

Bravo

AF:

0.800

Asia WGS

AF:

0.775

AC:

2697

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Age related macular degeneration 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Complement component 3 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.062

DANN

Benign

0.44

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