NM_001737.5:c.476+2890C>T

Variant names:

• chr5-39338256-G-A
• rs3822462
• NM_001737.5:c.476+2890C>T

Variant summary

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

The NM_001737.5(C9):​c.476+2890C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0928 in 152,120 control chromosomes in the GnomAD database, including 826 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 0.093 (826 hom., cov: 33)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C9	NM_001737.5	c.476+2890C>T		intron_variant	Intron 4 of 10	ENST00000263408.5	NP_001728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C9	ENST00000263408.5	c.476+2890C>T		intron_variant	Intron 4 of 10	1	NM_001737.5	ENSP00000263408.4

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14122 AN: 152000 Hom.: 825 Cov.: 33

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0519

Gnomad OTH AF: 0.0889

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

GnomAD4 genome AF: 0.0928 AC: 14118 AN: 152120 Hom.: 826 Cov.: 33 AF XY: 0.0916 AC XY: 6813 AN XY: 74376

African (AFR) AF: 0.170 AC: 7064 AN: 41462

American (AMR) AF: 0.101 AC: 1549 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3468

East Asian (EAS) AF: 0.106 AC: 548 AN: 5180

South Asian (SAS) AF: 0.0671 AC: 324 AN: 4828

European-Finnish (FIN) AF: 0.0646 AC: 684 AN: 10596

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0519 AC: 3531 AN: 68004

Other (OTH) AF: 0.0898 AC: 189 AN: 2104

Alfa AF: 0.0619 Hom.: 608

Bravo AF: 0.103

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.81
PhyloP100		0.11
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: rs3822462; hg19: chr5-39338358;