rs2305060

Positions:

• chr5-41203242-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000065.5(C6):​c.-12G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 1,613,624 control chromosomes in the GnomAD database, including 8,601 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (870 hom., cov: 32)
  • Exomes 𝑓: 0.10 (7731 hom.)
• Consequence: C6 NM_000065.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.427

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]

C6 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-41203242-C-T is Benign according to our data. Variant chr5-41203242-C-T is described in ClinVar as [Benign]. Clinvar id is 402459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C6	NM_000065.5	c.-12G>A		5_prime_UTR_variant	2/18	ENST00000337836.10	NP_000056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000337836.10	c.-12G>A		5_prime_UTR_variant	2/18	1	NM_000065.5	ENSP00000338861.5

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16393 AN: 152060 Hom.: 870 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0928

Gnomad OTH AF: 0.0914

GnomAD3 exomes AF: 0.101 AC: 25381 AN: 250750 Hom.: 1397 AF XY: 0.101 AC XY: 13639 AN XY: 135506

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.0843

Gnomad EAS exome AF: 0.108

Gnomad SAS exome AF: 0.111

Gnomad FIN exome AF: 0.0875

Gnomad NFE exome AF: 0.0911

Gnomad OTH exome AF: 0.0972

GnomAD4 exome AF: 0.100 AC: 146169 AN: 1461446 Hom.: 7731 Cov.: 32 AF XY: 0.100 AC XY: 72736 AN XY: 727078

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.117

Gnomad4 ASJ exome AF: 0.0819

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.114

Gnomad4 FIN exome AF: 0.0873

Gnomad4 NFE exome AF: 0.0964

Gnomad4 OTH exome AF: 0.103

GnomAD4 genome AF: 0.108 AC: 16409 AN: 152178 Hom.: 870 Cov.: 32 AF XY: 0.108 AC XY: 8002 AN XY: 74412

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.0864

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0936

Gnomad4 NFE AF: 0.0928

Gnomad4 OTH AF: 0.0909

Alfa AF: 0.0965 Hom.: 728

Bravo AF: 0.111

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.35

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: rs2305060; hg19: chr5-41203344; COSMIC: COSV54707270;