Genetic Variant C9:c.870+132C>T (chr5-39315643-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001737.5(C9):c.870+132C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 676,998 control chromosomes in the GnomAD database, including 40,786 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 0.29 ( 7247 hom., cov: 32)

Exomes 𝑓: 0.35 ( 33539 hom. )

Consequence

C9
NM_001737.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.95

Publications

7 publications found

Variant links:

Genes affected

C9 (HGNC:1358): (complement C9) This gene encodes the final component of the complement system. It participates in the formation of the Membrane Attack Complex (MAC). The MAC assembles on bacterial membranes to form a pore, permitting disruption of bacterial membrane organization. Mutations in this gene cause component C9 deficiency. [provided by RefSeq, Feb 2009]

C9 Gene-Disease associations (from GenCC):

complement component 9 deficiency
Inheritance: AR, Unknown Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

C9 links:

Genome browser will be placed here

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=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001737.5. 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
	C9	NM_001737.5	MANE Select	c.870+132C>T		intron	N/A	NP_001728.1	P02748

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
C9	ENST00000263408.5	TSL:1 MANE Select	c.870+132C>T	intron	N/A	ENSP00000263408.4	P02748
C9	ENST00000884641.1		c.954+132C>T	intron	N/A	ENSP00000554700.1
C9	ENST00000884639.1		c.870+132C>T	intron	N/A	ENSP00000554698.1

Frequencies

GnomAD3 genomes

AF:

0.289

AC:

43905

AN:

151816

Hom.:

7246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.403

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.192

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.406

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.348

AC:

182629

AN:

525064

Hom.:

33539

AF XY:

0.348

AC XY:

95873

AN XY:

275298

show subpopulations

African (AFR)

AF:

0.124

AC:

1692

AN:

13642

American (AMR)

AF:

0.250

AC:

4846

AN:

19398

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

4505

AN:

14950

East Asian (EAS)

AF:

0.152

AC:

4741

AN:

31282

South Asian (SAS)

AF:

0.338

AC:

15455

AN:

45790

European-Finnish (FIN)

AF:

0.418

AC:

15407

AN:

36892

Middle Eastern (MID)

AF:

0.273

AC:

579

AN:

2118

European-Non Finnish (NFE)

AF:

0.379

AC:

126125

AN:

332718

Other (OTH)

AF:

0.328

AC:

9279

AN:

28274

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

5597

11194

16792

22389

27986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1426

2852

4278

5704

7130

<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:

0.289

AC:

43906

AN:

151934

Hom.:

7247

Cov.:

AF XY:

0.290

AC XY:

21500

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.129

AC:

5349

AN:

41480

American (AMR)

AF:

0.256

AC:

3910

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1014

AN:

3468

East Asian (EAS)

AF:

0.192

AC:

993

AN:

5162

South Asian (SAS)

AF:

0.338

AC:

1630

AN:

4818

European-Finnish (FIN)

AF:

0.406

AC:

4266

AN:

10502

Middle Eastern (MID)

AF:

0.247

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.378

AC:

25702

AN:

67930

Other (OTH)

AF:

0.286

AC:

603

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1526

3051

4577

6102

7628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.341

Hom.:

37281

Bravo

AF:

0.269

Asia WGS

AF:

0.237

AC:

818

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.035

(source)

DANN

Benign

0.35

PhyloP100

-1.9

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