Genetic Variant C6:c.2102-50T>G (chr5-41154048-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.839

Publications

8 publications found

Variant links:

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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

C6 links:

ENSG00000307984 (HGNC:):

ENSG00000307984 links:

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ACMG classification

Classification was made for transcript

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

Sel.	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	P13671
	C6	NM_001115131.4		c.2102-50T>G		intron	N/A	NP_001108603.2	P13671

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C6	ENST00000337836.10	TSL:1 MANE Select	c.2102-50T>G	intron	N/A	ENSP00000338861.5	P13671
C6	ENST00000263413.7	TSL:1	c.2102-50T>G	intron	N/A	ENSP00000263413.3	P13671
C6	ENST00000905250.1		c.2159-50T>G	intron	N/A	ENSP00000575309.1

Frequencies

GnomAD3 genomes

AF:

0.864

AC:

131461

AN:

152092

Hom.:

56922

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.849

AC XY:

599275

AN XY:

706056

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

9320

18640

27959

37279

46599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20114

40228

60342

80456

100570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.864

AC:

131579

AN:

152210

Hom.:

56982

Cov.:

AF XY:

0.864

AC XY:

64287

AN XY:

74410

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

941

1883

2824

3766

4707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.43

PhyloP100

-0.84

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over