rs432001

Positions:

• chr19-6693672-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3	NM_000064.4	c.3155-185T>C		intron_variant		ENST00000245907.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3	ENST00000245907.11	c.3155-185T>C		intron_variant		1	NM_000064.4	P1

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

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.170

Alfa AF: 0.134 Hom.: 671

Bravo AF: 0.180

Asia WGS AF: 0.137 AC: 475 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.9
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs432001; hg19: chr19-6693683;