19-6685934-C-T

Variant names:

• chr19-6685934-C-T
• rs7257062
• NM_000064.4:c.3810+190G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000064.4(C3):​c.3810+190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,042 control chromosomes in the GnomAD database, including 15,876 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.45 (15876 hom., cov: 32)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.605
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with C3 anomaly

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• complement component 3 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Laboratory for Molecular Medicine
• C3 glomerulonephritis

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ENSG00000297005 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 19-6685934-C-T is Benign according to our data. Variant chr19-6685934-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237635.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000064.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	NM_000064.4	MANE Select	c.3810+190G>A		intron	N/A	NP_000055.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	ENST00000245907.11	TSL:1 MANE Select	c.3810+190G>A		intron	N/A	ENSP00000245907.4
	C3	ENST00000695654.1		c.2835+190G>A		intron	N/A	ENSP00000512085.1
	C3	ENST00000695653.1		c.1719+190G>A		intron	N/A	ENSP00000512084.1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68889 AN: 151924 Hom.: 15860 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.434

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.454 AC: 68952 AN: 152042 Hom.: 15876 Cov.: 32 AF XY: 0.459 AC XY: 34131 AN XY: 74320

African (AFR) AF: 0.453 AC: 18774 AN: 41456

American (AMR) AF: 0.425 AC: 6493 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3468

East Asian (EAS) AF: 0.714 AC: 3693 AN: 5172

South Asian (SAS) AF: 0.481 AC: 2316 AN: 4816

European-Finnish (FIN) AF: 0.505 AC: 5340 AN: 10574

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29375 AN: 67960

Other (OTH) AF: 0.438 AC: 925 AN: 2112

Alfa AF: 0.429 Hom.: 19062

Bravo AF: 0.451

Asia WGS AF: 0.557 AC: 1935 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.51
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7257062; hg19: chr19-6685945;