rs187875

Positions:

• chr5-39315643-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.870+132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 676,998 control chromosomes in the GnomAD database, including 40,786 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 0.29 (7247 hom., cov: 32)
  • Exomes 𝑓: 0.35 (33539 hom.)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C9	NM_001737.5	c.870+132C>T		intron_variant		ENST00000263408.5	NP_001728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C9	ENST00000263408.5	c.870+132C>T		intron_variant		1	NM_001737.5	ENSP00000263408	P2

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43905 AN: 151816 Hom.: 7246 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.348 AC: 182629 AN: 525064 Hom.: 33539 AF XY: 0.348 AC XY: 95873 AN XY: 275298

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.152

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.328

GnomAD4 genome AF: 0.289 AC: 43906 AN: 151934 Hom.: 7247 Cov.: 32 AF XY: 0.290 AC XY: 21500 AN XY: 74230

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.286

Alfa AF: 0.349 Hom.: 16631

Bravo AF: 0.269

Asia WGS AF: 0.237 AC: 818 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.035
DANN	Benign	0.35

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: rs187875; hg19: chr5-39315745;