chr19-6693672-A-G

Variant names:

• chr19-6693672-A-G
• rs432001
• NM_000064.4:c.3155-185T>C

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.3155-185T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 149,686 control chromosomes in the GnomAD database, including 2,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2770 hom., cov: 27)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.708
• Publications: 15 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: ClinGen, Labcorp Genetics (formerly Invitae)
• complement component 3 deficiency

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

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-6693672-A-G is Benign according to our data. Variant chr19-6693672-A-G is described in ClinVar as Benign. ClinVar VariationId is 1245079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	NM_000064.4	MANE Select	c.3155-185T>C		intron	N/A	NP_000055.2	P01024

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C3	ENST00000245907.11	TSL:1 MANE Select	c.3155-185T>C		intron	N/A	ENSP00000245907.4	P01024
	C3	ENST00000952696.1		c.3167-185T>C		intron	N/A	ENSP00000622755.1
	C3	ENST00000879543.1		c.3152-185T>C		intron	N/A	ENSP00000549602.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26290 AN: 149566 Hom.: 2764 Cov.: 27

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.176 AC: 26333 AN: 149686 Hom.: 2770 Cov.: 27 AF XY: 0.176 AC XY: 12851 AN XY: 73008

African (AFR) AF: 0.294 AC: 11917 AN: 40534

American (AMR) AF: 0.126 AC: 1902 AN: 15064

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 625 AN: 3444

East Asian (EAS) AF: 0.113 AC: 558 AN: 4956

South Asian (SAS) AF: 0.100 AC: 470 AN: 4690

European-Finnish (FIN) AF: 0.176 AC: 1803 AN: 10216

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8540 AN: 67498

Other (OTH) AF: 0.170 AC: 353 AN: 2082

Alfa AF: 0.138 Hom.: 1255

Bravo AF: 0.180

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		0.71
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: rs432001; hg19: chr19-6693683;