5-41233944-C-T

Variant names:

• chr5-41233944-C-T
• rs7443270
• ENST00000263413.7:c.-21+27250G>A

Variant summary

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

The ENST00000263413.7(C6):​c.-21+27250G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,866 control chromosomes in the GnomAD database, including 37,410 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 0.70 (37410 hom., cov: 32)
• Consequence: C6 ENST00000263413.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 4 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 (AFR) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263413.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C6	NM_001115131.4		c.-21+27250G>A		intron	N/A	NP_001108603.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C6	ENST00000263413.7	TSL:1	c.-21+27250G>A		intron	N/A	ENSP00000263413.3

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106345 AN: 151748 Hom.: 37390 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.659

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.701 AC: 106413 AN: 151866 Hom.: 37410 Cov.: 32 AF XY: 0.698 AC XY: 51806 AN XY: 74218

African (AFR) AF: 0.726 AC: 30115 AN: 41482

American (AMR) AF: 0.667 AC: 10174 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2311 AN: 3466

East Asian (EAS) AF: 0.557 AC: 2869 AN: 5152

South Asian (SAS) AF: 0.720 AC: 3468 AN: 4820

European-Finnish (FIN) AF: 0.668 AC: 7030 AN: 10524

Middle Eastern (MID) AF: 0.661 AC: 193 AN: 292

European-Non Finnish (NFE) AF: 0.710 AC: 48181 AN: 67868

Other (OTH) AF: 0.693 AC: 1459 AN: 2104

Alfa AF: 0.711 Hom.: 14060

Bravo AF: 0.697

Asia WGS AF: 0.639 AC: 2212 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		0.054
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7443270; hg19: chr5-41234046;