rs4245977

Positions:

• chr5-41195598-C-T

Variant summary

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

The NM_000065.5(C6):​c.587+194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,158 control chromosomes in the GnomAD database, including 875 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 (875 hom., cov: 32)
• Consequence: C6 NM_000065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.659

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6	NM_000065.5	c.587+194G>A		intron_variant		ENST00000337836.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6	ENST00000337836.10	c.587+194G>A		intron_variant		1	NM_000065.5	P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16434 AN: 152040 Hom.: 875 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0862

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0926

Gnomad OTH AF: 0.0912

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

GnomAD4 genome AF: 0.108 AC: 16450 AN: 152158 Hom.: 875 Cov.: 32 AF XY: 0.108 AC XY: 8013 AN XY: 74368

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0862

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0936

Gnomad4 NFE AF: 0.0926

Gnomad4 OTH AF: 0.0907

Alfa AF: 0.0969 Hom.: 936

Bravo AF: 0.111

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.57

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: rs4245977; hg19: chr5-41195700; COSMIC: COSV54718776; COSMIC: COSV54718776;