dbSNP rs1193963599: CGB7:p.Gly95Cys (chr19-49054506-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001385261.1(CGB7):c.283G>T(p.Gly95Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G95D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000074 ( 0 hom., cov: 19)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB7
NM_001385261.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.51

Publications

0 publications found

Variant links:

Genes affected

CGB7 (HGNC:16451): (chorionic gonadotropin subunit beta 7) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 7 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]

CGB7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1 link	c.283G>T	p.Gly95Cys	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2 link	c.283G>T	p.Gly95Cys	missense_variant	Exon 5 of 5		NP_149133.1	P0DN87A0A0F7RQF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CGB7	ENST00000684222.1 link	c.283G>T	p.Gly95Cys	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1	P0DN87
CGB7	ENST00000596965.5 link	c.283G>T	p.Gly95Cys	missense_variant	Exon 5 of 5	2		ENSP00000469076.1	P0DN87
CGB7	ENST00000597853.5 link	c.283G>T	p.Gly95Cys	missense_variant	Exon 5 of 5	2		ENSP00000470813.1	P0DN87

Frequencies

GnomAD3 genomes

AF:

0.00000739

AC:

AN:

135314

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.24e-7

AC:

AN:

1381154

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685760

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32548

American (AMR)

AF:

0.00

AC:

AN:

41520

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25084

East Asian (EAS)

AF:

0.00

AC:

AN:

38412

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49678

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3980

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1049828

Other (OTH)

AF:

0.00

AC:

AN:

57316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000739

AC:

AN:

135314

Hom.:

Cov.:

AF XY:

0.0000154

AC XY:

AN XY:

64726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

37286

American (AMR)

AF:

0.00

AC:

AN:

13312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3262

East Asian (EAS)

AF:

0.00

AC:

AN:

4630

South Asian (SAS)

AF:

0.000269

AC:

AN:

3718

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

302

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

61602

Other (OTH)

AF:

0.00

AC:

AN:

1728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.83

D;D;D

Eigen

Benign

0.17

Eigen_PC

Benign

0.0055

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.95

D;.;.

M_CAP

Pathogenic

0.29

MetaRNN

Pathogenic

0.98

D;D;D

MetaSVM

Pathogenic

0.81

PhyloP100

3.5

PROVEAN

Pathogenic

-8.0

D;.;.

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;.;.

Sift4G

Uncertain

0.0040

D;D;D

Vest4

0.79

MVP

0.86

MPC

2.3

ClinPred

0.99

GERP RS

1.8

Varity_R

0.86

gMVP

0.22

Mutation Taster

=80/20

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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rs1193963599

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over