rs4957374

Positions:

• chr5-41154048-A-C
• chr5-41154048-A-G
• chr5-41154048-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000065.5(C6):​c.2102-50T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.85 in 1,566,516 control chromosomes in the GnomAD database, including 567,101 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 0.86 (56982 hom., cov: 33)
  • Exomes 𝑓: 0.85 (510119 hom.)
• Consequence: C6 NM_000065.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.839

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C6	NM_000065.5	c.2102-50T>G		intron_variant		ENST00000337836.10	NP_000056.2
LOC105374739	XR_001742650.2	n.887-7265A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C6	ENST00000337836.10	c.2102-50T>G		intron_variant		1	NM_000065.5	ENSP00000338861	P1
C6	ENST00000263413.7	c.2102-50T>G		intron_variant		1		ENSP00000263413	P1
C6	ENST00000461473.1	n.134-50T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131461 AN: 152092 Hom.: 56922 Cov.: 33

Gnomad AFR AF: 0.893

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.849

Gnomad OTH AF: 0.879

GnomAD3 exomes AF: 0.858 AC: 209592 AN: 244180 Hom.: 90149 AF XY: 0.855 AC XY: 112963 AN XY: 132108

Gnomad AFR exome AF: 0.893

Gnomad AMR exome AF: 0.931

Gnomad ASJ exome AF: 0.887

Gnomad EAS exome AF: 0.794

Gnomad SAS exome AF: 0.844

Gnomad FIN exome AF: 0.833

Gnomad NFE exome AF: 0.847

Gnomad OTH exome AF: 0.863

GnomAD4 exome AF: 0.849 AC: 1200650 AN: 1414306 Hom.: 510119 Cov.: 23 AF XY: 0.849 AC XY: 599275 AN XY: 706056

Gnomad4 AFR exome AF: 0.892

Gnomad4 AMR exome AF: 0.927

Gnomad4 ASJ exome AF: 0.887

Gnomad4 EAS exome AF: 0.849

Gnomad4 SAS exome AF: 0.846

Gnomad4 FIN exome AF: 0.831

Gnomad4 NFE exome AF: 0.845

Gnomad4 OTH exome AF: 0.848

GnomAD4 genome AF: 0.864 AC: 131579 AN: 152210 Hom.: 56982 Cov.: 33 AF XY: 0.864 AC XY: 64287 AN XY: 74410

Gnomad4 AFR AF: 0.893

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.892

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.849

Gnomad4 OTH AF: 0.877

Alfa AF: 0.860 Hom.: 43711

Bravo AF: 0.870

Asia WGS AF: 0.801 AC: 2783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.43

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: rs4957374; hg19: chr5-41154150; COSMIC: COSV54716792; COSMIC: COSV54716792;