rs4957473

Positions:

• chr5-39343061-A-G
• chr5-39343061-A-T

Variant summary

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

The NM_001737.5(C9):​c.78-865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 152,066 control chromosomes in the GnomAD database, including 7,872 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 0.30 (7872 hom., cov: 32)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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=-0.93).
• 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	UniProt
C9	NM_001737.5	c.78-865T>C		intron_variant		ENST00000263408.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C9	ENST00000263408.5	c.78-865T>C		intron_variant		1	NM_001737.5	P2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45894 AN: 151948 Hom.: 7868 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.454

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.302 AC: 45918 AN: 152066 Hom.: 7872 Cov.: 32 AF XY: 0.305 AC XY: 22709 AN XY: 74370

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.454

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.301

Alfa AF: 0.360 Hom.: 13747

Bravo AF: 0.286

Asia WGS AF: 0.304 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.71
DANN	Benign	0.22

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: rs4957473; hg19: chr5-39343163;