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

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]

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C6	NM_000065.5	c.*321G>A		3_prime_UTR_variant	Exon 18 of 18	ENST00000337836.10	NP_000056.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000337836	c.*321G>A		3_prime_UTR_variant	Exon 18 of 18	1	NM_000065.5	ENSP00000338861.5
C6	ENST00000263413	c.*321G>A		3_prime_UTR_variant	Exon 18 of 18	1		ENSP00000263413.3
C6	ENST00000706654.1	n.1293G>A		non_coding_transcript_exon_variant	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

Gnomad4 AFR exome AF: 0.821 AC: 5676 AN: 6910

Gnomad4 AMR exome AF: 0.701 AC: 5975 AN: 8526

Gnomad4 ASJ exome AF: 0.604 AC: 3091 AN: 5120

Gnomad4 EAS exome AF: 0.726 AC: 8685 AN: 11958

Gnomad4 SAS exome AF: 0.587 AC: 8608 AN: 14664

Gnomad4 FIN exome AF: 0.412 AC: 3154 AN: 7658

Gnomad4 NFE exome AF: 0.470 AC: 45665 AN: 97108

Gnomad4 Remaining exome 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

Gnomad4 AFR AF: 0.819 AC: 0.818524 AN: 0.818524

Gnomad4 AMR AF: 0.659 AC: 0.658537 AN: 0.658537

Gnomad4 ASJ AF: 0.613 AC: 0.613191 AN: 0.613191

Gnomad4 EAS AF: 0.683 AC: 0.683191 AN: 0.683191

Gnomad4 SAS AF: 0.598 AC: 0.598043 AN: 0.598043

Gnomad4 FIN AF: 0.409 AC: 0.408633 AN: 0.408633

Gnomad4 NFE AF: 0.468 AC: 0.468161 AN: 0.468161

Gnomad4 OTH AF: 0.585 AC: 0.585227 AN: 0.585227

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.4
DANN	Benign	0.62
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

Publications

LitVar

Other links and lift over

dbSNP: rs9200; hg19: chr5-41142606;