1-56956799-G-T

Variant names:

• chr1-56956799-G-T
• rs150022116
• NM_000066.4:c.361C>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_000066.4(C8B):​c.361C>A​(p.Arg121Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,792 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 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: C8B NM_000066.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.36
• Publications: 6 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 1-56956799-G-T is Benign according to our data. Variant chr1-56956799-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1523047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.36 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8B	NM_000066.4	c.361C>A	p.Arg121Arg	synonymous_variant	Exon 3 of 12	ENST00000371237.9	NP_000057.3
C8B	NM_001278543.2	c.205C>A	p.Arg69Arg	synonymous_variant	Exon 4 of 13		NP_001265472.2
C8B	NM_001278544.2	c.175C>A	p.Arg59Arg	synonymous_variant	Exon 4 of 13		NP_001265473.2
C8B	XM_047429957.1	c.361C>A	p.Arg121Arg	synonymous_variant	Exon 3 of 7		XP_047285913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8B	ENST00000371237.9	c.361C>A	p.Arg121Arg	synonymous_variant	Exon 3 of 12	1	NM_000066.4	ENSP00000360281.4

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152002 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000242

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: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000915 AC: 23 AN: 251312 AF XY: 0.000103

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000110 AC: 161 AN: 1461790 Hom.: 0 Cov.: 30 AF XY: 0.000111 AC XY: 81 AN XY: 727210

African (AFR) AF: 0.0000896 AC: 3 AN: 33474

American (AMR) AF: 0.0000447 AC: 2 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000220 AC: 19 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000118 AC: 131 AN: 1111942

Other (OTH) AF: 0.0000994 AC: 6 AN: 60390

GnomAD4 genome AF: 0.0000592 AC: 9 AN: 152002 Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4 AN XY: 74226

African (AFR) AF: 0.0000242 AC: 1 AN: 41396

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000146 Hom.: 1

Bravo AF: 0.0000529

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 17, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.79
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs150022116; hg19: chr1-57422472;