rs1421094

Positions:

• chr5-39355489-G-A
• chr5-39355489-G-T

Variant summary

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

The NM_001737.5(C9):​c.77+8899C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 151,596 control chromosomes in the GnomAD database, including 10,144 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 0.37 (10144 hom., cov: 30)
• Consequence: C9 NM_001737.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.885

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C9	NM_001737.5	c.77+8899C>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.77+8899C>T		intron_variant		1	NM_001737.5	ENSP00000263408	P2

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55439 AN: 151478 Hom.: 10145 Cov.: 30

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.366 AC: 55460 AN: 151596 Hom.: 10144 Cov.: 30 AF XY: 0.368 AC XY: 27221 AN XY: 74022

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.415

Alfa AF: 0.329 Hom.: 1992

Bravo AF: 0.364

Asia WGS AF: 0.337 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.91
DANN	Benign	0.62

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: rs1421094; hg19: chr5-39355591;