Genetic Variant NM_001378156.1:c.-23-115_-23-112dupGATG (chr1-22659292-A-AGATG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001378156.1(C1QB):c.-23-115_-23-112dupGATG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 645,344 control chromosomes in the GnomAD database, including 7,484 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 1799 hom., cov: 0)

Exomes 𝑓: 0.13 ( 5685 hom. )

Consequence

C1QB
NM_001378156.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.22

Publications

0 publications found

Variant links:

Genes affected

C1QB (HGNC:1242): (complement C1q B chain) This gene encodes the B-chain polypeptide of serum complement subcomponent C1q, which associates with C1r and C1s to yield the first component of the serum complement system. C1q is composed of 18 polypeptide chains which include 6 A-chains, 6 B-chains, and 6 C-chains. Each chain contains an N-terminal collagen-like region and a C-terminal C1q globular domain. C1q deficiency is associated with lupus erythematosus and glomerulonephritis. [provided by RefSeq, Dec 2016]

C1QB Gene-Disease associations (from GenCC):

C1Q deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

C1QB links:

ENSG00000308848 (HGNC:):

ENSG00000308848 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 1-22659292-A-AGATG is Benign according to our data. Variant chr1-22659292-A-AGATG is described in ClinVar as [Benign]. Clinvar id is 1283735.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
C1QB	NM_001378156.1 link	c.-23-115_-23-112dupGATG	intron_variant	Intron 1 of 2	ENST00000509305.6	NP_001365085.1
C1QB	NM_000491.5 link	c.-17-115_-17-112dupGATG	intron_variant	Intron 1 of 2		NP_000482.3	P02746A0A024RAB9
C1QB	NM_001371184.3 link	c.-23-115_-23-112dupGATG	intron_variant	Intron 2 of 3		NP_001358113.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C1QB	ENST00000509305.6 link	c.-23-148_-23-147insGATG		intron_variant	Intron 1 of 2	1	NM_001378156.1	ENSP00000423689.1		D6R934

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

20089

AN:

128552

Hom.:

1791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.0714

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.150

GnomAD4 exome

AF:

0.134

AC:

69363

AN:

516662

Hom.:

5685

AF XY:

0.133

AC XY:

36245

AN XY:

272296

show subpopulations

African (AFR)

AF:

0.197

AC:

2781

AN:

14096

American (AMR)

AF:

0.188

AC:

5040

AN:

26838

Ashkenazi Jewish (ASJ)

AF:

0.0925

AC:

1482

AN:

16022

East Asian (EAS)

AF:

0.339

AC:

8807

AN:

25978

South Asian (SAS)

AF:

0.130

AC:

6474

AN:

49676

European-Finnish (FIN)

AF:

0.169

AC:

6267

AN:

36988

Middle Eastern (MID)

AF:

0.0998

AC:

214

AN:

2144

European-Non Finnish (NFE)

AF:

0.109

AC:

34486

AN:

316888

Other (OTH)

AF:

0.136

AC:

3812

AN:

28032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

2658

5316

7975

10633

13291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.156

AC:

20112

AN:

128682

Hom.:

1799

Cov.:

AF XY:

0.157

AC XY:

9685

AN XY:

61632

show subpopulations

African (AFR)

AF:

0.199

AC:

6364

AN:

31986

American (AMR)

AF:

0.166

AC:

2174

AN:

13060

Ashkenazi Jewish (ASJ)

AF:

0.101

AC:

334

AN:

3302

East Asian (EAS)

AF:

0.336

AC:

1261

AN:

3750

South Asian (SAS)

AF:

0.123

AC:

442

AN:

3584

European-Finnish (FIN)

AF:

0.161

AC:

1285

AN:

7972

Middle Eastern (MID)

AF:

0.0570

AC:

AN:

228

European-Non Finnish (NFE)

AF:

0.127

AC:

7900

AN:

62176

Other (OTH)

AF:

0.152

AC:

271

AN:

1788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

739

1477

2216

2954

3693

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0711

Hom.:

126

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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NM_001378156.1:c.-23-115_-23-112dupGATG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over