Genetic Variant CGB3:p.Cys120Cys (chr19-49023024-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_000737.5(CGB3):c.360C>T(p.Cys120Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 17)

Exomes 𝑓: 0.00031 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

CGB3
NM_000737.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.01

Publications

0 publications found

Variant links:

Genes affected

CGB3 (HGNC:1886): (chorionic gonadotropin subunit beta 3) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 3 subunit of chorionic gonadotropin (CG). Glycoprotein hormones are heterodimers consisting of a common alpha subunit and an unique beta subunit which confers biological specificity. CG is produced by the trophoblastic cells of the placenta and stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy. The beta subunit of CG is encoded by 6 genes which are arranged in tandem and inverted pairs on chromosome 19q13.3 and contiguous with the luteinizing hormone beta subunit gene. [provided by RefSeq, Jul 2008]

CGB3 links:

ENSG00000267335 (HGNC:):

ENSG00000267335 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 19-49023024-G-A is Benign according to our data. Variant chr19-49023024-G-A is described in CliVar as Likely_benign. Clinvar id is 2650230.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-49023024-G-A is described in CliVar as Likely_benign. Clinvar id is 2650230.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-49023024-G-A is described in CliVar as Likely_benign. Clinvar id is 2650230.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB3	NM_000737.5 link	c.360C>T	p.Cys120Cys	synonymous_variant	Exon 3 of 3	ENST00000357383.4	NP_000728.1	P0DN86-1A0A0F7RQP8
LOC124904738	XR_007067288.1 link	n.*209G>A		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CGB3	ENST00000357383.4 link	c.360C>T	p.Cys120Cys	synonymous_variant	Exon 3 of 3	1	NM_000737.5	ENSP00000349954.2	P0DN86-1
ENSG00000267335	ENST00000591656.1 link	c.318C>T	p.Cys106Cys	synonymous_variant	Exon 3 of 3	2		ENSP00000466140.1	K7ELM3
ENSG00000267335	ENST00000604577.1 link	c.*122C>T		downstream_gene_variant		1		ENSP00000474022.1	S4R385

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

197

AN:

133726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00430

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000712

Gnomad ASJ

AF:

0.00914

Gnomad EAS

AF:

0.000416

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000803

Gnomad OTH

AF:

0.000567

GnomAD2 exomes

AF:

0.000501

AC:

AN:

73860

AF XY:

0.000616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000413

Gnomad ASJ exome

AF:

0.00823

Gnomad EAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.000153

Gnomad NFE exome

AF:

0.000105

Gnomad OTH exome

AF:

0.000451

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000312

AC:

431

AN:

1382396

Hom.:

Cov.:

AF XY:

0.000292

AC XY:

200

AN XY:

685658

show subpopulations

African (AFR)

AF:

0.00407

AC:

123

AN:

30198

American (AMR)

AF:

0.000723

AC:

AN:

34574

Ashkenazi Jewish (ASJ)

AF:

0.00680

AC:

161

AN:

23674

East Asian (EAS)

AF:

0.000589

AC:

AN:

39020

South Asian (SAS)

AF:

0.0000377

AC:

AN:

79548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49718

Middle Eastern (MID)

AF:

0.000260

AC:

AN:

3848

European-Non Finnish (NFE)

AF:

0.0000488

AC:

AN:

1064694

Other (OTH)

AF:

0.000753

AC:

AN:

57122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00147

AC:

197

AN:

133826

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

AN XY:

64132

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00429

AC:

150

AN:

34990

American (AMR)

AF:

0.000711

AC:

AN:

12650

Ashkenazi Jewish (ASJ)

AF:

0.00914

AC:

AN:

3284

East Asian (EAS)

AF:

0.000417

AC:

AN:

4800

South Asian (SAS)

AF:

0.00

AC:

AN:

3838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0000803

AC:

AN:

62250

Other (OTH)

AF:

0.000561

AC:

AN:

1784

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.342

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00156

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CGB3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.094

(source)

DANN

Benign

0.75

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over