dbSNP rs11569536: C3:c.3810+46C>T (chr19-6686078-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000064.4(C3):c.3810+46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,600,060 control chromosomes in the GnomAD database, including 3,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 291 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3430 hom. )

Consequence

C3
NM_000064.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0790

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-6686078-G-A is Benign according to our data. Variant chr19-6686078-G-A is described in ClinVar as [Benign]. Clinvar id is 1258093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C3	NM_000064.4 link	c.3810+46C>T		intron_variant	Intron 29 of 40	ENST00000245907.11	NP_000055.2	P01024V9HWA9B4DR57

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C3	ENST00000245907.11 link	c.3810+46C>T		intron_variant	Intron 29 of 40	1	NM_000064.4	ENSP00000245907.4		P01024

Frequencies

GnomAD3 genomes

AF:

0.0596

AC:

9073

AN:

152144

Hom.:

290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0635

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.0322

Gnomad ASJ

AF:

0.0300

Gnomad EAS

AF:

0.00904

Gnomad SAS

AF:

0.0298

Gnomad FIN

AF:

0.0575

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0705

Gnomad OTH

AF:

0.0445

GnomAD3 exomes

AF:

0.0489

AC:

12284

AN:

251374

Hom.:

354

AF XY:

0.0489

AC XY:

6645

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.0644

Gnomad AMR exome

AF:

0.0220

Gnomad ASJ exome

AF:

0.0296

Gnomad EAS exome

AF:

0.0106

Gnomad SAS exome

AF:

0.0312

Gnomad FIN exome

AF:

0.0574

Gnomad NFE exome

AF:

0.0661

Gnomad OTH exome

AF:

0.0452

GnomAD4 exome

AF:

0.0650

AC:

94108

AN:

1447798

Hom.:

3430

Cov.:

AF XY:

0.0640

AC XY:

46144

AN XY:

720898

show subpopulations

Gnomad4 AFR exome

AF:

0.0643

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.0324

Gnomad4 EAS exome

AF:

0.00770

Gnomad4 SAS exome

AF:

0.0318

Gnomad4 FIN exome

AF:

0.0595

Gnomad4 NFE exome

AF:

0.0728

Gnomad4 OTH exome

AF:

0.0614

GnomAD4 genome

AF:

0.0596

AC:

9079

AN:

152262

Hom.:

291

Cov.:

AF XY:

0.0583

AC XY:

4337

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.0634

Gnomad4 AMR

AF:

0.0321

Gnomad4 ASJ

AF:

0.0300

Gnomad4 EAS

AF:

0.00906

Gnomad4 SAS

AF:

0.0299

Gnomad4 FIN

AF:

0.0575

Gnomad4 NFE

AF:

0.0705

Gnomad4 OTH

AF:

0.0441

Alfa

AF:

0.0632

Hom.:

499

Bravo

AF:

0.0568

Asia WGS

AF:

0.0200

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.6

DANN

Benign

0.51

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