rs4400166

Variant names:

• chr5-41188189-G-A
• rs4400166
• NM_000065.5:c.588-1981C>T

Variant summary

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

The NM_000065.5(C6):​c.588-1981C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,836 control chromosomes in the GnomAD database, including 21,571 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 0.53 (21571 hom., cov: 32)
• Consequence: C6 NM_000065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6	NM_000065.5	c.588-1981C>T		intron_variant	Intron 5 of 17	ENST00000337836.10	NP_000056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000337836.10	c.588-1981C>T		intron_variant	Intron 5 of 17	1	NM_000065.5	ENSP00000338861.5
C6	ENST00000263413.7	c.588-1981C>T		intron_variant	Intron 5 of 17	1		ENSP00000263413.3
C6	ENST00000433294.2	c.588-1981C>T		intron_variant	Intron 6 of 6	5		ENSP00000401578.2
C6	ENST00000706655.1	n.861-1981C>T		intron_variant	Intron 5 of 10

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80011 AN: 151718 Hom.: 21555 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.527 AC: 80072 AN: 151836 Hom.: 21571 Cov.: 32 AF XY: 0.524 AC XY: 38872 AN XY: 74188

African (AFR) AF: 0.592 AC: 24503 AN: 41414

American (AMR) AF: 0.435 AC: 6623 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1398 AN: 3462

East Asian (EAS) AF: 0.240 AC: 1243 AN: 5170

South Asian (SAS) AF: 0.406 AC: 1960 AN: 4828

European-Finnish (FIN) AF: 0.570 AC: 6025 AN: 10566

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.540 AC: 36611 AN: 67844

Other (OTH) AF: 0.510 AC: 1075 AN: 2106

Alfa AF: 0.521 Hom.: 65239

Bravo AF: 0.515

Asia WGS AF: 0.306 AC: 1063 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.57
DANN	Benign	0.21
PhyloP100		-0.13
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: rs4400166; hg19: chr5-41188291;