dbSNP rs1425612647: C8B:p.Pro573Pro (chr1-56929461-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000066.4(C8B):c.1719T>C(p.Pro573Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

C8B
NM_000066.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.448

Publications

0 publications found

Variant links:

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)

C8B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 1-56929461-A-G is Benign according to our data. Variant chr1-56929461-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1950344.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.448 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000066.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C8B	NM_000066.4	MANE Select	c.1719T>C	p.Pro573Pro	synonymous	Exon 12 of 12	NP_000057.3	P07358
C8B	NM_001278543.2		c.1563T>C	p.Pro521Pro	synonymous	Exon 13 of 13	NP_001265472.2
C8B	NM_001278544.2		c.1533T>C	p.Pro511Pro	synonymous	Exon 13 of 13	NP_001265473.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C8B	ENST00000371237.9	TSL:1 MANE Select	c.1719T>C	p.Pro573Pro	synonymous	Exon 12 of 12	ENSP00000360281.4	P07358
C8B	ENST00000696164.1		c.1719T>C	p.Pro573Pro	synonymous	Exon 13 of 13	ENSP00000512454.1	A0A8Q3WL56
C8B	ENST00000875298.1		c.1719T>C	p.Pro573Pro	synonymous	Exon 13 of 13	ENSP00000545357.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460746

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726682

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33432

American (AMR)

AF:

0.00

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86200

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4972

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111904

Other (OTH)

AF:

0.00

AC:

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41440

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.1

(source)

DANN

Benign

0.73

PhyloP100

0.45

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over