rs3776526

chr5-39353620-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001737.5(C9):c.77+10768A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,190 control chromosomes in the GnomAD database, including 3,981 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 0.20 (3981 hom., cov: 32)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

Genes affected

C9 (HGNC:1358): (complement C9) This gene encodes the final component of the complement system. It 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 component C9 deficiency. [provided by RefSeq, Feb 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C9	NM_001737.5	c.77+10768A>G		intron_variant		ENST00000263408.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C9	ENST00000263408.5	c.77+10768A>G		intron_variant		1	NM_001737.5	P2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30893 AN: 152072 Hom.: 3982 Cov.: 32

Gnomad AFR AF: 0.0524

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.171

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.203 AC: 30893 AN: 152190 Hom.: 3981 Cov.: 32 AF XY: 0.205 AC XY: 15263 AN XY: 74408

Gnomad4 AFR AF: 0.0523

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.171

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.173

Alfa AF: 0.262 Hom.: 1138

Bravo AF: 0.181

Asia WGS AF: 0.152 AC: 525 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	6.0
Dann	Benign	0.71

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: rs3776526; hg19: chr5-39353722;