5-41185259-T-C

Variant names:

• chr5-41185259-T-C
• rs4245976
• NM_000065.5:c.726+811A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000065.5(C6):​c.726+811A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 152,154 control chromosomes in the GnomAD database, including 57,385 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 0.87 (57385 hom., cov: 31)
• Consequence: C6 NM_000065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• complement component 6 deficiency

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6	NM_000065.5	c.726+811A>G		intron_variant	Intron 6 of 17	ENST00000337836.10	NP_000056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000337836.10	c.726+811A>G		intron_variant	Intron 6 of 17	1	NM_000065.5	ENSP00000338861.5
C6	ENST00000263413.7	c.726+811A>G		intron_variant	Intron 6 of 17	1		ENSP00000263413.3
C6	ENST00000475349.5	n.125+1008A>G		intron_variant	Intron 1 of 5	3
C6	ENST00000706655.1	n.999+811A>G		intron_variant	Intron 6 of 10

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131930 AN: 152036 Hom.: 57348 Cov.: 31

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.873

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.899

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.834

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.880

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

GnomAD4 genome AF: 0.868 AC: 132019 AN: 152154 Hom.: 57385 Cov.: 31 AF XY: 0.867 AC XY: 64484 AN XY: 74390

African (AFR) AF: 0.858 AC: 35614 AN: 41504

American (AMR) AF: 0.923 AC: 14104 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 3121 AN: 3470

East Asian (EAS) AF: 0.754 AC: 3897 AN: 5170

South Asian (SAS) AF: 0.835 AC: 4017 AN: 4810

European-Finnish (FIN) AF: 0.828 AC: 8776 AN: 10596

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59605 AN: 68006

Other (OTH) AF: 0.878 AC: 1856 AN: 2114

Alfa AF: 0.870 Hom.: 8264

Bravo AF: 0.874

Asia WGS AF: 0.758 AC: 2628 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.51
DANN	Benign	0.69
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4245976; hg19: chr5-41185361;