rs696758

Positions:

• chr5-39331114-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C9	NM_001737.5	c.615+562C>T		intron_variant		ENST00000263408.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C9	ENST00000263408.5	c.615+562C>T		intron_variant		1	NM_001737.5	P2

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

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0702

Gnomad4 FIN AF: 0.0656

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0827 Hom.: 734

Bravo AF: 0.149

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.097
DANN	Benign	0.54

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: rs696758; hg19: chr5-39331216;