rs9332457

chr5-41185070-C-A

Variant summary

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

The NM_000065.5(C6):c.726+1000G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 151,950 control chromosomes in the GnomAD database, including 13,704 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 0.42 (13704 hom., cov: 32)
• Consequence: C6 NM_000065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533

Genes affected

C6 (HGNC:1339): (complement C6) This gene encodes a component of the complement cascade. The encoded protein is part of the membrane attack complex that can be incorporated into the cell membrane and cause cell lysis. Mutations in this gene are associated with complement component-6 deficiency. Transcript variants encoding the same protein have been described.[provided by RefSeq, Nov 2012]

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 (AFR) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6	NM_000065.5	c.726+1000G>T		intron_variant		ENST00000337836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6	ENST00000337836.10	c.726+1000G>T		intron_variant		1	NM_000065.5	P1
C6	ENST00000263413.7	c.726+1000G>T		intron_variant		1		P1
C6	ENST00000475349.5	n.125+1197G>T		intron_variant, non_coding_transcript_variant		3
C6	ENST00000706655.1	n.999+1000G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63803 AN: 151830 Hom.: 13696 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.423

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

GnomAD4 genome AF: 0.420 AC: 63849 AN: 151950 Hom.: 13704 Cov.: 32 AF XY: 0.417 AC XY: 30970 AN XY: 74244

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.327

Gnomad4 ASJ AF: 0.317

Gnomad4 EAS AF: 0.128

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.419

Alfa AF: 0.428 Hom.: 6913

Bravo AF: 0.405

Asia WGS AF: 0.215 AC: 746 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	5.8
Dann	Benign	0.49

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: rs9332457; hg19: chr5-41185172; COSMIC: COSV54712701;