chr5-41217587-G-A

Variant names:

• chr5-41217587-G-A
• rs7444800
• ENST00000263413.7:c.-20-14337C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.9).
• 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 rank	MANE	Protein	UniProt
C6	NM_001115131.4	c.-20-14337C>T		intron_variant	Intron 1 of 17		NP_001108603.2
C6	XM_011514114.4	c.8-14337C>T		intron_variant	Intron 1 of 18		XP_011512416.1
C6	XM_006714496.5	c.8-14337C>T		intron_variant	Intron 1 of 18		XP_006714559.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000263413.7	c.-20-14337C>T		intron_variant	Intron 1 of 17	1		ENSP00000263413.3

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

African (AFR) AF: 0.701 AC: 29077 AN: 41482

American (AMR) AF: 0.695 AC: 10583 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2351 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2836 AN: 5170

South Asian (SAS) AF: 0.726 AC: 3503 AN: 4822

European-Finnish (FIN) AF: 0.682 AC: 7222 AN: 10588

Middle Eastern (MID) AF: 0.658 AC: 192 AN: 292

European-Non Finnish (NFE) AF: 0.735 AC: 49934 AN: 67930

Other (OTH) AF: 0.712 AC: 1504 AN: 2112

Alfa AF: 0.722 Hom.: 28730

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
PhyloP100		-0.46
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: rs7444800; hg19: chr5-41217689;