Variant rs10411506 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.1479+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,603,574 control chromosomes in the GnomAD database, including 19,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1909 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17160 hom. )

Consequence

C3
NM_000064.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.29

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=-0.8).

BP6

Variant 19-6710937-G-A is Benign according to our data. Variant chr19-6710937-G-A is described in ClinVar as [Benign]. Clinvar id is 1230447.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 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.1479+50C>T		intron_variant		ENST00000245907.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3	ENST00000245907.11 linkuse as main transcript	c.1479+50C>T		intron_variant		1	NM_000064.4	P1

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22305

AN:

151966

Hom.:

1910

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.171

AC:

42750

AN:

250716

Hom.:

4533

AF XY:

0.173

AC XY:

23492

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.118

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.196

Gnomad EAS exome

AF:

0.428

Gnomad SAS exome

AF:

0.225

Gnomad FIN exome

AF:

0.195

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.143

AC:

208199

AN:

1451490

Hom.:

17160

Cov.:

AF XY:

0.146

AC XY:

105363

AN XY:

722682

show subpopulations

Gnomad4 AFR exome

AF:

0.122

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.200

Gnomad4 EAS exome

AF:

0.411

Gnomad4 SAS exome

AF:

0.217

Gnomad4 FIN exome

AF:

0.199

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.156

GnomAD4 genome

AF:

0.147

AC:

22305

AN:

152084

Hom.:

1909

Cov.:

AF XY:

0.153

AC XY:

11354

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.121

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.429

Gnomad4 SAS

AF:

0.253

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.129

Gnomad4 OTH

AF:

0.130

Alfa

AF:

0.147

Hom.:

371

Bravo

AF:

0.139

Asia WGS

AF:

0.297

AC:

1031

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

-0.80

CADD

Benign

0.29

DANN

Benign

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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