Variant 6-32028747-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001002029.4(C4B):c.3285C>A(p.Gly1095Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,544,536 control chromosomes in the GnomAD database, including 36,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 4578 hom., cov: 21)

Exomes 𝑓: 0.14 ( 31576 hom. )

Consequence

C4B
NM_001002029.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.647

Variant links:

Genes affected

C4B (HGNC:1324): (complement C4B (Chido/Rodgers blood group)) This gene encodes the basic form of complement factor 4, and together with the C4A gene, is part of the classical activation pathway. The protein is expressed as a single chain precursor which is proteolytically cleaved into a trimer of alpha, beta, and gamma chains prior to secretion. The trimer provides a surface for interaction between the antigen-antibody complex and other complement components. The alpha chain may be cleaved to release C4 anaphylatoxin, a mediator of local inflammation. Deficiency of this protein is associated with systemic lupus erythematosus. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. Varying haplotypes of this gene cluster exist, such that individuals may have 1, 2, or 3 copies of this gene. In addition, this gene exists as a long form and a short form due to the presence or absence of a 6.4 kb endogenous HERV-K retrovirus in intron 9. [provided by RefSeq, May 2020]

C4B links:

C4B (HGNC:):

C4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 6-32028747-C-A is Benign according to our data. Variant chr6-32028747-C-A is described in ClinVar as [Benign]. Clinvar id is 2688520.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.647 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C4B	NM_001002029.4 linkuse as main transcript	c.3285C>A	p.Gly1095Gly	synonymous_variant	26/41	ENST00000435363.7	NP_001002029.3	P0C0L4P0C0L5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
C4B	ENST00000435363.7 linkuse as main transcript	c.3285C>A	p.Gly1095Gly	synonymous_variant	26/41	1	NM_001002029.4	ENSP00000415941.2	P0C0L5
C4B	ENST00000425700.3 linkuse as main transcript	c.3285C>A	p.Gly1095Gly	synonymous_variant	26/40	1		ENSP00000391933.2	F5GXS0
C4B	ENST00000647698.1 linkuse as main transcript	c.1989C>A	p.Gly663Gly	synonymous_variant	16/31			ENSP00000497270.1	A0A3B3ISA6
C4B	ENST00000648821.1 linkuse as main transcript	n.1898C>A		non_coding_transcript_exon_variant	13/27

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

25694

AN:

135546

Hom.:

4565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.366

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.184

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.201

Gnomad FIN

AF:

0.0373

Gnomad MID

AF:

0.238

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.149

AC:

33769

AN:

226874

Hom.:

5637

AF XY:

0.150

AC XY:

18483

AN XY:

123036

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.104

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.243

Gnomad FIN exome

AF:

0.0448

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.139

AC:

196178

AN:

1408876

Hom.:

31576

Cov.:

AF XY:

0.141

AC XY:

98443

AN XY:

700612

show subpopulations

Gnomad4 AFR exome

AF:

0.378

Gnomad4 AMR exome

AF:

0.129

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.163

Gnomad4 SAS exome

AF:

0.232

Gnomad4 FIN exome

AF:

0.0450

Gnomad4 NFE exome

AF:

0.128

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.190

AC:

25734

AN:

135660

Hom.:

4578

Cov.:

AF XY:

0.188

AC XY:

12341

AN XY:

65548

show subpopulations

Gnomad4 AFR

AF:

0.366

Gnomad4 AMR

AF:

0.184

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.148

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.0373

Gnomad4 NFE

AF:

0.119

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.148

Hom.:

656

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied by a panel of primary immunodeficiencies. Number of patients: 18. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.5

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over