dbSNP rs1055021: C7:c.2350+155C>A (chr5-40980064-C-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_000587.4(C7):c.2350+155C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 516,112 control chromosomes in the GnomAD database, including 3,602 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 0.091 ( 873 hom., cov: 32)

Exomes 𝑓: 0.12 ( 2729 hom. )

Consequence

C7
NM_000587.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0990

Publications

3 publications found

Variant links:

Genes affected

C7 (HGNC:1346): (complement C7) This gene encodes a serum glycoprotein that forms a membrane attack complex together with complement components C5b, C6, C8, and C9 as part of the terminal complement pathway of the innate immune system. The protein encoded by this gene contains a cholesterol-dependent cytolysin/membrane attack complex/perforin-like (CDC/MACPF) domain and belongs to a large family of structurally related molecules that form pores involved in host immunity and bacterial pathogenesis. This protein initiates membrane attack complex formation by binding the C5b-C6 subcomplex and inserts into the phospholipid bilayer, serving as a membrane anchor. Mutations in this gene are associated with a rare disorder called C7 deficiency. [provided by RefSeq, Nov 2016]

C7 Gene-Disease associations (from GenCC):

complement component 7 deficiency
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)

C7 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=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C7	NM_000587.4 link	c.2350+155C>A		intron_variant	Intron 17 of 17	ENST00000313164.10	NP_000578.2	P10643Q05CI3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C7	ENST00000313164.10 link	c.2350+155C>A		intron_variant	Intron 17 of 17	1	NM_000587.4	ENSP00000322061.9		P10643

Frequencies

GnomAD3 genomes

AF:

0.0912

AC:

13867

AN:

152100

Hom.:

873

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0288

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.149

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.0799

Gnomad FIN

AF:

0.0884

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.113

GnomAD4 exome

AF:

0.116

AC:

42348

AN:

363894

Hom.:

2729

Cov.:

AF XY:

0.116

AC XY:

21459

AN XY:

185228

show subpopulations

African (AFR)

AF:

0.0311

AC:

316

AN:

10152

American (AMR)

AF:

0.159

AC:

1835

AN:

11574

Ashkenazi Jewish (ASJ)

AF:

0.189

AC:

2091

AN:

11090

East Asian (EAS)

AF:

0.225

AC:

5969

AN:

26516

South Asian (SAS)

AF:

0.106

AC:

1484

AN:

14038

European-Finnish (FIN)

AF:

0.0904

AC:

2501

AN:

27680

Middle Eastern (MID)

AF:

0.144

AC:

243

AN:

1684

European-Non Finnish (NFE)

AF:

0.106

AC:

25402

AN:

239740

Other (OTH)

AF:

0.117

AC:

2507

AN:

21420

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1784

3568

5352

7136

8920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

372

744

1116

1488

1860

<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:

0.0911

AC:

13864

AN:

152218

Hom.:

873

Cov.:

AF XY:

0.0927

AC XY:

6896

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0288

AC:

1198

AN:

41554

American (AMR)

AF:

0.148

AC:

2265

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.186

AC:

644

AN:

3470

East Asian (EAS)

AF:

0.186

AC:

959

AN:

5154

South Asian (SAS)

AF:

0.0806

AC:

389

AN:

4826

European-Finnish (FIN)

AF:

0.0884

AC:

938

AN:

10606

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6953

AN:

68008

Other (OTH)

AF:

0.112

AC:

237

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

610

1219

1829

2438

3048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

158

316

474

632

790

<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:

0.0406

Hom.:

Bravo

AF:

0.0962

Asia WGS

AF:

0.114

AC:

398

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

(source)

DANN

Benign

0.68

PhyloP100

0.099

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over