Variant 19-6697818-G-T 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.2441-24C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 1,604,534 control chromosomes in the GnomAD database, including 330,681 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 33347 hom., cov: 28)

Exomes 𝑓: 0.64 ( 297334 hom. )

Consequence

C3
NM_000064.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -4.54

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=-0.83).

BP6

Variant 19-6697818-G-T is Benign according to our data. Variant chr19-6697818-G-T is described in ClinVar as [Benign]. Clinvar id is 1192552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.82 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.2441-24C>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.2441-24C>A		intron_variant		1	NM_000064.4	ENSP00000245907.4		P01024

Frequencies

GnomAD3 genomes

AF:

0.660

AC:

99912

AN:

151486

Hom.:

33309

Cov.:

show subpopulations

Gnomad AFR

AF:

0.706

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.736

Gnomad ASJ

AF:

0.613

Gnomad EAS

AF:

0.840

Gnomad SAS

AF:

0.714

Gnomad FIN

AF:

0.568

Gnomad MID

AF:

0.674

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.677

GnomAD3 exomes

AF:

0.671

AC:

160972

AN:

239922

Hom.:

54928

AF XY:

0.663

AC XY:

86001

AN XY:

129648

show subpopulations

Gnomad AFR exome

AF:

0.702

Gnomad AMR exome

AF:

0.809

Gnomad ASJ exome

AF:

0.596

Gnomad EAS exome

AF:

0.836

Gnomad SAS exome

AF:

0.708

Gnomad FIN exome

AF:

0.563

Gnomad NFE exome

AF:

0.614

Gnomad OTH exome

AF:

0.662

GnomAD4 exome

AF:

0.636

AC:

924179

AN:

1452930

Hom.:

297334

Cov.:

AF XY:

0.636

AC XY:

459563

AN XY:

722256

show subpopulations

Gnomad4 AFR exome

AF:

0.713

Gnomad4 AMR exome

AF:

0.798

Gnomad4 ASJ exome

AF:

0.592

Gnomad4 EAS exome

AF:

0.865

Gnomad4 SAS exome

AF:

0.706

Gnomad4 FIN exome

AF:

0.566

Gnomad4 NFE exome

AF:

0.617

Gnomad4 OTH exome

AF:

0.648

GnomAD4 genome

AF:

0.660

AC:

100006

AN:

151604

Hom.:

33347

Cov.:

AF XY:

0.662

AC XY:

49024

AN XY:

74084

show subpopulations

Gnomad4 AFR

AF:

0.707

Gnomad4 AMR

AF:

0.736

Gnomad4 ASJ

AF:

0.613

Gnomad4 EAS

AF:

0.841

Gnomad4 SAS

AF:

0.713

Gnomad4 FIN

AF:

0.568

Gnomad4 NFE

AF:

0.615

Gnomad4 OTH

AF:

0.672

Alfa

AF:

0.629

Hom.:

29337

Bravo

AF:

0.675

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Age related macular degeneration 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

-0.83

CADD

Benign

0.055

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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