rs7444800

chr5-41217587-G-Achr5-41217587-G-C

Variant summary

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

The ENST00000263413.7(C6):c.-20-14337C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 152,012 control chromosomes in the GnomAD database, including 38,358 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 0.71 (38358 hom., cov: 32)
• Consequence: C6 ENST00000263413.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C6	NM_001115131.4	c.-20-14337C>T		intron_variant
C6	XM_006714496.5	c.8-14337C>T		intron_variant
C6	XM_011514114.4	c.8-14337C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6	ENST00000263413.7	c.-20-14337C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107745 AN: 151894 Hom.: 38335 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.709 AC: 107816 AN: 152012 Hom.: 38358 Cov.: 32 AF XY: 0.707 AC XY: 52511 AN XY: 74290

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.726

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.735

Gnomad4 OTH AF: 0.712

Alfa AF: 0.722 Hom.: 21238

Bravo AF: 0.704

Asia WGS AF: 0.636 AC: 2207 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.88
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7444800; hg19: chr5-41217689;