rs3776541

Positions:

• chr5-39290703-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001737.5(C9):​c.1417-1752G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 151,538 control chromosomes in the GnomAD database, including 1,070 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 0.11 (1070 hom., cov: 32)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C9	NM_001737.5	c.1417-1752G>C		intron_variant		ENST00000263408.5	NP_001728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C9	ENST00000263408.5	c.1417-1752G>C		intron_variant		1	NM_001737.5	ENSP00000263408	P2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16238 AN: 151420 Hom.: 1067 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0802

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0540

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0729

Gnomad FIN AF: 0.0659

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.107 AC: 16240 AN: 151538 Hom.: 1070 Cov.: 32 AF XY: 0.105 AC XY: 7806 AN XY: 74050

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0540

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0729

Gnomad4 FIN AF: 0.0659

Gnomad4 NFE AF: 0.0648

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0896 Hom.: 98

Bravo AF: 0.121

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.43

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: rs3776541; hg19: chr5-39290805;