5-41213233-C-G

Position:

• chr5-41213233-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000337836.10(C6):​c.-21+143G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 216,400 control chromosomes in the GnomAD database, including 7,793 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 0.23 (4989 hom., cov: 32)
  • Exomes 𝑓: 0.29 (2804 hom.)
• Consequence: C6 ENST00000337836.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C6	NM_000065.5	c.-21+143G>C		intron_variant		ENST00000337836.10	NP_000056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000337836.10	c.-21+143G>C		intron_variant		1	NM_000065.5	ENSP00000338861	P1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35147 AN: 151780 Hom.: 4991 Cov.: 32

Gnomad AFR AF: 0.0754

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.289 AC: 18621 AN: 64500 Hom.: 2804 AF XY: 0.288 AC XY: 9088 AN XY: 31610

Gnomad4 AFR exome AF: 0.0540

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.207

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.208

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.231 AC: 35137 AN: 151900 Hom.: 4989 Cov.: 32 AF XY: 0.233 AC XY: 17307 AN XY: 74228

Gnomad4 AFR AF: 0.0752

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.249

Alfa AF: 0.183 Hom.: 493

Bravo AF: 0.207

Asia WGS AF: 0.137 AC: 477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	9.9
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: rs10512766; hg19: chr5-41213335;