rs696758

Variant names:

• chr5-39331114-G-A
• rs696758
• NM_001737.5:c.615+562C>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.615+562C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,124 control chromosomes in the GnomAD database, including 1,908 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 0.13 (1908 hom., cov: 32)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 7 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001737.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C9	NM_001737.5	MANE Select	c.615+562C>T		intron	N/A	NP_001728.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C9	ENST00000263408.5	TSL:1 MANE Select	c.615+562C>T		intron	N/A	ENSP00000263408.4
	C9	ENST00000509186.6	TSL:3	c.543+562C>T		intron	N/A	ENSP00000512235.1
	C9	ENST00000695880.1		c.615+562C>T		intron	N/A	ENSP00000512236.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19917 AN: 152006 Hom.: 1905 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0702

Gnomad FIN AF: 0.0656

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.131 AC: 19921 AN: 152124 Hom.: 1908 Cov.: 32 AF XY: 0.128 AC XY: 9527 AN XY: 74380

African (AFR) AF: 0.269 AC: 11163 AN: 41454

American (AMR) AF: 0.158 AC: 2415 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0501 AC: 174 AN: 3470

East Asian (EAS) AF: 0.106 AC: 548 AN: 5178

South Asian (SAS) AF: 0.0702 AC: 338 AN: 4814

European-Finnish (FIN) AF: 0.0656 AC: 696 AN: 10614

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.0623 AC: 4233 AN: 67990

Other (OTH) AF: 0.126 AC: 265 AN: 2110

Alfa AF: 0.0918 Hom.: 1217

Bravo AF: 0.149

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.097
DANN	Benign	0.54
PhyloP100		-2.3
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: rs696758; hg19: chr5-39331216;