rs11569585

Variant names:

• chr19-6677788-G-A
• rs11569585
• NM_000064.4:c.*94C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-6677788-G-A
• chr19-6677788-G-C
• chr19-6677788-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000064.4(C3):​c.*94C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0451 in 1,492,622 control chromosomes in the GnomAD database, including 1,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.053 (251 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1482 hom.)
• Consequence: C3 NM_000064.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.14
• 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-6677788-G-A is Benign according to our data. Variant chr19-6677788-G-A is described in ClinVar as Benign. ClinVar VariationId is 1280962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0821 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.*94C>T		3_prime_UTR	Exon 41 of 41	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.*94C>T		3_prime_UTR	Exon 41 of 41	ENSP00000245907.4	P01024
	C3	ENST00000695651.1		n.3434C>T		non_coding_transcript_exon	Exon 28 of 28
	C3	ENST00000952696.1		c.*94C>T		downstream_gene	N/A	ENSP00000622755.1

Frequencies

GnomAD3 genomes AF: 0.0532 AC: 8100 AN: 152152 Hom.: 245 Cov.: 32

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0340

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.00693

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0439

Gnomad OTH AF: 0.0407

GnomAD4 exome AF: 0.0442 AC: 59239 AN: 1340352 Hom.: 1482 Cov.: 20 AF XY: 0.0447 AC XY: 29976 AN XY: 670818

African (AFR) AF: 0.0821 AC: 2553 AN: 31106

American (AMR) AF: 0.0252 AC: 1072 AN: 42588

Ashkenazi Jewish (ASJ) AF: 0.0426 AC: 1068 AN: 25082

East Asian (EAS) AF: 0.00645 AC: 251 AN: 38894

South Asian (SAS) AF: 0.0530 AC: 4371 AN: 82534

European-Finnish (FIN) AF: 0.0582 AC: 2634 AN: 45268

Middle Eastern (MID) AF: 0.0425 AC: 210 AN: 4942

European-Non Finnish (NFE) AF: 0.0439 AC: 44525 AN: 1013532

Other (OTH) AF: 0.0453 AC: 2555 AN: 56406

GnomAD4 genome AF: 0.0534 AC: 8129 AN: 152270 Hom.: 251 Cov.: 32 AF XY: 0.0527 AC XY: 3923 AN XY: 74452

African (AFR) AF: 0.0845 AC: 3508 AN: 41528

American (AMR) AF: 0.0339 AC: 519 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.00694 AC: 36 AN: 5184

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4824

European-Finnish (FIN) AF: 0.0559 AC: 593 AN: 10612

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0439 AC: 2988 AN: 68036

Other (OTH) AF: 0.0408 AC: 86 AN: 2110

Alfa AF: 0.0457 Hom.: 225

Bravo AF: 0.0527

Asia WGS AF: 0.0350 AC: 120 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.0
DANN	Benign	0.95
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs11569585; hg19: chr19-6677799;