1-56953934-T-C

Position:

• chr1-56953934-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
C8B	NM_000066.4	c.533+752A>G		intron_variant		ENST00000371237.9	NP_000057.3
C8B	NM_001278543.2	c.377+752A>G		intron_variant			NP_001265472.2
C8B	NM_001278544.2	c.347+752A>G		intron_variant			NP_001265473.2
C8B	XM_047429957.1	c.533+752A>G		intron_variant			XP_047285913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C8B	ENST00000371237.9	c.533+752A>G		intron_variant		1	NM_000066.4	ENSP00000360281	P1

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

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.595

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.703

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.654

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

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

LitVar

Other links and lift over

dbSNP: rs647571; hg19: chr1-57419607; COSMIC: COSV64777019; COSMIC: COSV64777019;