rs4957374

Variant names:

• chr5-41154048-A-C
• rs4957374
• NM_000065.5:c.2102-50T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-41154048-A-C
• chr5-41154048-A-G
• chr5-41154048-A-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.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
• Publications: 8 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

ENSG00000307984 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.2102-50T>G		intron	N/A	NP_000056.2
	C6	NM_001115131.4		c.2102-50T>G		intron	N/A	NP_001108603.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C6	ENST00000337836.10	TSL:1 MANE Select	c.2102-50T>G		intron	N/A	ENSP00000338861.5
	C6	ENST00000263413.7	TSL:1	c.2102-50T>G		intron	N/A	ENSP00000263413.3
	C6	ENST00000461473.1	TSL:3	n.134-50T>G		intron	N/A

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

GnomAD2 exomes AF: 0.858 AC: 209592 AN: 244180 AF XY: 0.855

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 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

African (AFR) AF: 0.892 AC: 28960 AN: 32476

American (AMR) AF: 0.927 AC: 41012 AN: 44226

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 22812 AN: 25728

East Asian (EAS) AF: 0.849 AC: 33250 AN: 39170

South Asian (SAS) AF: 0.846 AC: 71783 AN: 84864

European-Finnish (FIN) AF: 0.831 AC: 44071 AN: 53014

Middle Eastern (MID) AF: 0.862 AC: 4683 AN: 5430

European-Non Finnish (NFE) AF: 0.845 AC: 904284 AN: 1070676

Other (OTH) AF: 0.848 AC: 49795 AN: 58722

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

African (AFR) AF: 0.893 AC: 37097 AN: 41530

American (AMR) AF: 0.903 AC: 13812 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3096 AN: 3472

East Asian (EAS) AF: 0.797 AC: 4124 AN: 5174

South Asian (SAS) AF: 0.847 AC: 4087 AN: 4828

European-Finnish (FIN) AF: 0.828 AC: 8766 AN: 10586

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.849 AC: 57736 AN: 68012

Other (OTH) AF: 0.877 AC: 1855 AN: 2116

Alfa AF: 0.861 Hom.: 52333

Bravo AF: 0.870

Asia WGS AF: 0.801 AC: 2783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.43
PhyloP100		-0.84
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: rs4957374; hg19: chr5-41154150; COSMIC: COSV54716792; COSMIC: COSV54716792;