rs647571

Variant names:

• chr1-56953934-T-C
• rs647571
• NM_000066.4:c.533+752A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000066.4(C8B):​c.533+752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,042 control chromosomes in the GnomAD database, including 35,325 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.68 (35325 hom., cov: 32)
• Consequence: C8B NM_000066.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 5 publications found

Genes affected

C8B (HGNC:1353): (complement C8 beta chain) This gene encodes one of the three subunits of the complement component 8 (C8) protein. C8 is composed of equimolar amounts of alpha, beta and gamma subunits, which are encoded by three separate genes. C8 is one component of the membrane attack complex, which mediates cell lysis, and it initiates membrane penetration of the complex. This protein mediates the interaction of C8 with the C5b-7 membrane attack complex precursor. In humans deficiency of this protein is associated with increased risk of meningococcal infections. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2013]

C8B Gene-Disease associations (from GenCC):

• type II complement component 8 deficiency

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8B	NM_000066.4	c.533+752A>G		intron_variant	Intron 4 of 11	ENST00000371237.9	NP_000057.3
C8B	NM_001278543.2	c.377+752A>G		intron_variant	Intron 5 of 12		NP_001265472.2
C8B	NM_001278544.2	c.347+752A>G		intron_variant	Intron 5 of 12		NP_001265473.2
C8B	XM_047429957.1	c.533+752A>G		intron_variant	Intron 4 of 6		XP_047285913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8B	ENST00000371237.9	c.533+752A>G		intron_variant	Intron 4 of 11	1	NM_000066.4	ENSP00000360281.4

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103062 AN: 151924 Hom.: 35293 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.678 AC: 103152 AN: 152042 Hom.: 35325 Cov.: 32 AF XY: 0.681 AC XY: 50608 AN XY: 74322

African (AFR) AF: 0.743 AC: 30812 AN: 41484

American (AMR) AF: 0.561 AC: 8574 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2232 AN: 3468

East Asian (EAS) AF: 0.595 AC: 3068 AN: 5152

South Asian (SAS) AF: 0.757 AC: 3643 AN: 4812

European-Finnish (FIN) AF: 0.703 AC: 7431 AN: 10570

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45279 AN: 67968

Other (OTH) AF: 0.654 AC: 1383 AN: 2114

Alfa AF: 0.675 Hom.: 5891

Bravo AF: 0.662

Asia WGS AF: 0.661 AC: 2298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.63
PhyloP100		-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: rs647571; hg19: chr1-57419607; COSMIC: COSV64777019; COSMIC: COSV64777019;