Variant chr19-6685293-G-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.3811-147C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.397 in 739,252 control chromosomes in the GnomAD database, including 61,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11067 hom., cov: 31)

Exomes 𝑓: 0.40 ( 50148 hom. )

Consequence

C3
NM_000064.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.503

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:

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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=-0.84).

BP6

Variant 19-6685293-G-C is Benign according to our data. Variant chr19-6685293-G-C is described in ClinVar as [Benign]. Clinvar id is 1261016.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.613 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.3811-147C>G		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.3811-147C>G		intron_variant		1	NM_000064.4	ENSP00000245907.4		P01024

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56864

AN:

151844

Hom.:

11050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.410

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.631

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.478

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.381

Gnomad OTH

AF:

0.366

GnomAD4 exome

AF:

0.403

AC:

236758

AN:

587288

Hom.:

50148

AF XY:

0.404

AC XY:

127330

AN XY:

315144

show subpopulations

Gnomad4 AFR exome

AF:

0.296

Gnomad4 AMR exome

AF:

0.405

Gnomad4 ASJ exome

AF:

0.330

Gnomad4 EAS exome

AF:

0.669

Gnomad4 SAS exome

AF:

0.451

Gnomad4 FIN exome

AF:

0.469

Gnomad4 NFE exome

AF:

0.374

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.375

AC:

56935

AN:

151964

Hom.:

11067

Cov.:

AF XY:

0.382

AC XY:

28360

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.298

Gnomad4 AMR

AF:

0.383

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.631

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.478

Gnomad4 NFE

AF:

0.381

Gnomad4 OTH

AF:

0.372

Alfa

AF:

0.379

Hom.:

6336

Bravo

AF:

0.368

Asia WGS

AF:

0.507

AC:

1760

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	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.0

DANN

Benign

0.43

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