rs1620073

Variant names:

• chr1-56912477-C-T
• rs1620073
• NM_000562.3:c.1455C>T
• C8A p.Arg485Arg

Your query was ambiguous. Multiple possible variants found:

• chr1-56912477-C-T
• chr1-56912477-C-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000562.3(C8A):​c.1455C>T​(p.Arg485Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0623 in 1,614,082 control chromosomes in the GnomAD database, including 4,779 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1237 hom., cov: 33)
  • Exomes 𝑓: 0.058 (3542 hom.)
• Consequence: C8A NM_000562.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0140
• Publications: 6 publications found

Genes affected

C8A (HGNC:1352): (complement C8 alpha chain) C8 is a component of the complement system and contains three polypeptides, alpha, beta and gamma. This gene encodes the alpha subunit of C8. C8 participates in the formation of the membrane attack complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause complement C8 alpha-gamma deficiency. [provided by RefSeq, Nov 2008]

C8A Gene-Disease associations (from GenCC):

• type I complement component 8 deficiency

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-56912477-C-T is Benign according to our data. Variant chr1-56912477-C-T is described in ClinVar as Benign. ClinVar VariationId is 402462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.014 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000562.3. 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
	C8A	NM_000562.3	MANE Select	c.1455C>T	p.Arg485Arg	synonymous	Exon 10 of 11	NP_000553.1	P07357

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C8A	ENST00000361249.4	TSL:1 MANE Select	c.1455C>T	p.Arg485Arg	synonymous	Exon 10 of 11	ENSP00000354458.3	P07357
	C8A	ENST00000695678.1		c.1455C>T	p.Arg485Arg	synonymous	Exon 10 of 11	ENSP00000512098.1	A0A8Q3WL79
	C8A	ENST00000854265.1		c.1431C>T	p.Arg477Arg	synonymous	Exon 10 of 11	ENSP00000524324.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15577 AN: 152120 Hom.: 1235 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0470

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0459

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.0756 AC: 19007 AN: 251306 AF XY: 0.0752

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.0917

Gnomad ASJ exome AF: 0.0454

Gnomad EAS exome AF: 0.0518

Gnomad FIN exome AF: 0.0483

Gnomad NFE exome AF: 0.0456

Gnomad OTH exome AF: 0.0711

GnomAD4 exome AF: 0.0581 AC: 84892 AN: 1461844 Hom.: 3542 Cov.: 33 AF XY: 0.0598 AC XY: 43481 AN XY: 727226

African (AFR) AF: 0.228 AC: 7621 AN: 33474

American (AMR) AF: 0.0928 AC: 4150 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0431 AC: 1126 AN: 26136

East Asian (EAS) AF: 0.0650 AC: 2581 AN: 39700

South Asian (SAS) AF: 0.132 AC: 11412 AN: 86258

European-Finnish (FIN) AF: 0.0459 AC: 2451 AN: 53416

Middle Eastern (MID) AF: 0.112 AC: 647 AN: 5768

European-Non Finnish (NFE) AF: 0.0457 AC: 50792 AN: 1111974

Other (OTH) AF: 0.0681 AC: 4112 AN: 60394

GnomAD4 genome AF: 0.102 AC: 15599 AN: 152238 Hom.: 1237 Cov.: 33 AF XY: 0.102 AC XY: 7597 AN XY: 74450

African (AFR) AF: 0.216 AC: 8948 AN: 41510

American (AMR) AF: 0.108 AC: 1657 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3466

East Asian (EAS) AF: 0.0517 AC: 267 AN: 5168

South Asian (SAS) AF: 0.139 AC: 669 AN: 4824

European-Finnish (FIN) AF: 0.0470 AC: 499 AN: 10628

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0459 AC: 3121 AN: 68026

Other (OTH) AF: 0.102 AC: 216 AN: 2112

Alfa AF: 0.0580 Hom.: 699

Bravo AF: 0.110

Asia WGS AF: 0.107 AC: 374 AN: 3478

EpiCase AF: 0.0480

EpiControl AF: 0.0511

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.5
DANN	Benign	0.40
PhyloP100		-0.014
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1620073;

hg19: chr1-57378150;

COSMIC: COSV63484443;