chr1-56894777-T-C

Variant names:

• chr1-56894777-T-C
• rs6699859
• NM_000562.3:c.1096+8610T>C

Variant summary

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

The NM_000562.3(C8A):​c.1096+8610T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,046 control chromosomes in the GnomAD database, including 43,252 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 0.75 (43252 hom., cov: 31)
• Consequence: C8A NM_000562.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 5 publications found

Genes affected

C8A (HGNC:1352): (complement C8 alpha chain) C8 is a component of the complement system and contains three polypeptides, alpha, beta and gamma. This gene encodes the alpha subunit of C8. C8 participates in the formation of the membrane attack complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause complement C8 alpha-gamma deficiency. [provided by RefSeq, Nov 2008]

C8A Gene-Disease associations (from GenCC):

• type I complement component 8 deficiency

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C8A	NM_000562.3	c.1096+8610T>C		intron_variant	Intron 7 of 10	ENST00000361249.4	NP_000553.1
C8A	XM_017002234.2	c.*630T>C		3_prime_UTR_variant	Exon 8 of 8		XP_016857723.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C8A	ENST00000361249.4	c.1096+8610T>C		intron_variant	Intron 7 of 10	1	NM_000562.3	ENSP00000354458.3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113472 AN: 151928 Hom.: 43203 Cov.: 31

Gnomad AFR AF: 0.875

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.747 AC: 113580 AN: 152046 Hom.: 43252 Cov.: 31 AF XY: 0.750 AC XY: 55713 AN XY: 74312

African (AFR) AF: 0.875 AC: 36305 AN: 41508

American (AMR) AF: 0.663 AC: 10103 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2292 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5137 AN: 5152

South Asian (SAS) AF: 0.876 AC: 4217 AN: 4814

European-Finnish (FIN) AF: 0.693 AC: 7322 AN: 10570

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45968 AN: 67972

Other (OTH) AF: 0.714 AC: 1511 AN: 2116

Alfa AF: 0.692 Hom.: 61149

Bravo AF: 0.746

Asia WGS AF: 0.921 AC: 3202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.18
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: rs6699859; hg19: chr1-57360450;