chr19-6696167-G-A

Variant names:

• chr19-6696167-G-A
• rs10410674
• NM_000064.4:c.2950+212C>T

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.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
• Publications: 1 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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.2950+212C>T		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.2950+212C>T		intron	N/A	ENSP00000245907.4
	C3	ENST00000695654.1		c.2074+212C>T		intron	N/A	ENSP00000512085.1
	C3	ENST00000695652.1		c.2827+212C>T		intron	N/A	ENSP00000512083.1

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

African (AFR) AF: 0.243 AC: 9294 AN: 38290

American (AMR) AF: 0.474 AC: 6750 AN: 14232

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1618 AN: 3444

East Asian (EAS) AF: 0.401 AC: 1935 AN: 4824

South Asian (SAS) AF: 0.382 AC: 1715 AN: 4486

European-Finnish (FIN) AF: 0.350 AC: 3154 AN: 9018

Middle Eastern (MID) AF: 0.540 AC: 148 AN: 274

European-Non Finnish (NFE) AF: 0.416 AC: 27798 AN: 66782

Other (OTH) AF: 0.409 AC: 799 AN: 1952

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

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	-0.94
CADD	Benign	2.6
DANN	Benign	0.59
PhyloP100		-0.55
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: rs10410674; hg19: chr19-6696178;