chr5-41142504-C-T

Position:

• chr5-41142504-C-T

Variant summary

Our verdict is Benign. Variant got -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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
C6	NM_000065.5	c.*321G>A		3_prime_UTR_variant	18/18	ENST00000337836.10
LOC105374739	XR_001742650.2	n.887-18809C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C6	ENST00000337836.10	c.*321G>A		3_prime_UTR_variant	18/18	1	NM_000065.5	P1
C6	ENST00000263413.7	c.*321G>A		3_prime_UTR_variant	18/18	1		P1
C6	ENST00000706654.1	n.1293G>A		non_coding_transcript_exon_variant	3/3

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

Gnomad4 AMR exome AF: 0.701

Gnomad4 ASJ exome AF: 0.604

Gnomad4 EAS exome AF: 0.726

Gnomad4 SAS exome AF: 0.587

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.470

Gnomad4 OTH exome AF: 0.533

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

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.683

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.585

Alfa AF: 0.509 Hom.: 20477

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

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;