rs3776526

Variant names:

• chr5-39353620-T-C
• rs3776526
• NM_001737.5:c.77+10768A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

C9 Gene-Disease associations (from GenCC):

• complement component 9 deficiency

  Inheritance: Unknown, AR Classification: STRONG, MODERATE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000289699 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C9	NM_001737.5	c.77+10768A>G		intron_variant	Intron 1 of 10	ENST00000263408.5	NP_001728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C9	ENST00000263408.5	c.77+10768A>G		intron_variant	Intron 1 of 10	1	NM_001737.5	ENSP00000263408.4

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

African (AFR) AF: 0.0523 AC: 2172 AN: 41558

American (AMR) AF: 0.180 AC: 2745 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 594 AN: 3466

East Asian (EAS) AF: 0.110 AC: 572 AN: 5190

South Asian (SAS) AF: 0.206 AC: 992 AN: 4818

European-Finnish (FIN) AF: 0.370 AC: 3913 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.285 AC: 19340 AN: 67976

Other (OTH) AF: 0.173 AC: 364 AN: 2110

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
PhyloP100		0.17
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: rs3776526; hg19: chr5-39353722;