5-41142504-C-T

Variant names:

• chr5-41142504-C-T
• rs9200
• NM_000065.5:c.*321G>A

Variant summary

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

The NM_000065.5(C6):​c.*321G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 314,002 control chromosomes in the GnomAD database, including 53,074 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 0.60 (28781 hom., cov: 32)
  • Exomes 𝑓: 0.53 (24293 hom.)
• Consequence: C6 NM_000065.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.825
• Publications: 18 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

LOC105374739 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000065.5. 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_000065.5	MANE Select	c.*321G>A		3_prime_UTR	Exon 18 of 18	NP_000056.2
	C6	NM_001115131.4		c.*321G>A		3_prime_UTR	Exon 18 of 18	NP_001108603.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C6	ENST00000337836.10	TSL:1 MANE Select	c.*321G>A		3_prime_UTR	Exon 18 of 18	ENSP00000338861.5
	C6	ENST00000263413.7	TSL:1	c.*321G>A		3_prime_UTR	Exon 18 of 18	ENSP00000263413.3
	C6	ENST00000706654.1		n.1293G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90376 AN: 151804 Hom.: 28721 Cov.: 32

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.586

GnomAD4 exome AF: 0.532 AC: 86258 AN: 162080 Hom.: 24293 Cov.: 0 AF XY: 0.535 AC XY: 44807 AN XY: 83724

African (AFR) AF: 0.821 AC: 5676 AN: 6910

American (AMR) AF: 0.701 AC: 5975 AN: 8526

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 3091 AN: 5120

East Asian (EAS) AF: 0.726 AC: 8685 AN: 11958

South Asian (SAS) AF: 0.587 AC: 8608 AN: 14664

European-Finnish (FIN) AF: 0.412 AC: 3154 AN: 7658

Middle Eastern (MID) AF: 0.541 AC: 369 AN: 682

European-Non Finnish (NFE) AF: 0.470 AC: 45665 AN: 97108

Other (OTH) AF: 0.533 AC: 5035 AN: 9454

GnomAD4 genome AF: 0.596 AC: 90503 AN: 151922 Hom.: 28781 Cov.: 32 AF XY: 0.594 AC XY: 44098 AN XY: 74222

African (AFR) AF: 0.819 AC: 33936 AN: 41460

American (AMR) AF: 0.659 AC: 10044 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2129 AN: 3472

East Asian (EAS) AF: 0.683 AC: 3528 AN: 5164

South Asian (SAS) AF: 0.598 AC: 2873 AN: 4804

European-Finnish (FIN) AF: 0.409 AC: 4298 AN: 10518

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31805 AN: 67936

Other (OTH) AF: 0.585 AC: 1236 AN: 2112

Alfa AF: 0.548 Hom.: 40339

Bravo AF: 0.628

Asia WGS AF: 0.641 AC: 2229 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.4
DANN	Benign	0.62
PhyloP100		0.82
Mutation Taster		=99/1	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: rs9200; hg19: chr5-41142606;