rs10410674

chr19-6696167-G-Achr19-6696167-G-C

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.2950+212C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 144,196 control chromosomes in the GnomAD database, including 10,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (10245 hom., cov: 22)
• Consequence: C3 NM_000064.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.546

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=-0.94).
• BP6: Variant 19-6696167-G-A is Benign according to our data. Variant chr19-6696167-G-A is described in ClinVar as [Benign]. Clinvar id is 1287554.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C3	NM_000064.4	c.2950+212C>T		intron_variant		ENST00000245907.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C3	ENST00000245907.11	c.2950+212C>T		intron_variant		1	NM_000064.4	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 53462 AN: 144124 Hom.: 10245 Cov.: 22

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.527

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.371 AC: 53475 AN: 144196 Hom.: 10245 Cov.: 22 AF XY: 0.372 AC XY: 25912 AN XY: 69596

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.409

Alfa AF: 0.241 Hom.: 610

Bravo AF: 0.369

Asia WGS AF: 0.378 AC: 1312 AN: 3472

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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	2.6
Dann	Benign	0.59

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: rs10410674; hg19: chr19-6696178;