rs700228

Variant names:

• chr5-39361753-G-A
• rs700228
• NM_001737.5:c.77+2635C>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.77+2635C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0435 in 152,152 control chromosomes in the GnomAD database, including 322 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 0.043 (322 hom., cov: 32)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C9	NM_001737.5	c.77+2635C>T		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+2635C>T		intron_variant	Intron 1 of 10	1	NM_001737.5	ENSP00000263408.4

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6598 AN: 152034 Hom.: 321 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.0389

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.00189

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0326

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

GnomAD4 genome AF: 0.0435 AC: 6613 AN: 152152 Hom.: 322 Cov.: 32 AF XY: 0.0415 AC XY: 3088 AN XY: 74396

African (AFR) AF: 0.119 AC: 4947 AN: 41470

American (AMR) AF: 0.0245 AC: 375 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.0388 AC: 201 AN: 5178

South Asian (SAS) AF: 0.0288 AC: 139 AN: 4824

European-Finnish (FIN) AF: 0.00189 AC: 20 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 843 AN: 68008

Other (OTH) AF: 0.0323 AC: 68 AN: 2106

Alfa AF: 0.0212 Hom.: 126

Bravo AF: 0.0487

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.93
DANN	Benign	0.51
PhyloP100		0.030
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: rs700228; hg19: chr5-39361855;