19-49054542-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001385261.1(CGB7):c.247C>T(p.Arg83Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000893 in 1,232,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB7
NM_001385261.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.72

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1 link	c.247C>T	p.Arg83Cys	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2 link	c.247C>T	p.Arg83Cys	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.247C>T	p.Arg83Cys	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1	P0DN87
CGB7	ENST00000596965.5 link	c.247C>T	p.Arg83Cys	missense_variant	Exon 5 of 5	2		ENSP00000469076.1	P0DN87
CGB7	ENST00000597853.5 link	c.247C>T	p.Arg83Cys	missense_variant	Exon 5 of 5	2		ENSP00000470813.1	P0DN87

Frequencies

GnomAD3 genomes

AF:

0.00000755

AC:

AN:

132510

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000272

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000160

AC:

AN:

62552

AF XY:

0.0000316

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000432

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000893

AC:

AN:

1232184

Hom.:

Cov.:

AF XY:

0.00000816

AC XY:

AN XY:

612980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30482

American (AMR)

AF:

0.00

AC:

AN:

36012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23404

East Asian (EAS)

AF:

0.00

AC:

AN:

35750

South Asian (SAS)

AF:

0.00

AC:

AN:

76084

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42770

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3744

European-Non Finnish (NFE)

AF:

0.0000118

AC:

AN:

931512

Other (OTH)

AF:

0.00

AC:

AN:

52426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

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:

0.00000755

AC:

AN:

132510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

63240

show subpopulations

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

African (AFR)

AF:

0.0000272

AC:

AN:

36822

American (AMR)

AF:

0.00

AC:

AN:

13202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3196

East Asian (EAS)

AF:

0.00

AC:

AN:

4538

South Asian (SAS)

AF:

0.00

AC:

AN:

3608

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

296

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59938

Other (OTH)

AF:

0.00

AC:

AN:

1724

⚠️ 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: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000742

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 27, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.247C>T (p.R83C) alteration is located in exon 3 (coding exon 3) of the CGB7 gene. This alteration results from a C to T substitution at nucleotide position 247, causing the arginine (R) at amino acid position 83 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.79

D;D;D

Eigen

Benign

-0.051

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.97

D;.;.

M_CAP

Pathogenic

0.39

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Uncertain

0.75

PhyloP100

1.7

PROVEAN

Pathogenic

-5.9

D;.;.

REVEL

Uncertain

0.61

Sift

Uncertain

0.0070

D;.;.

Sift4G

Benign

0.12

T;T;T

Vest4

0.48

MVP

0.79

MPC

2.5

ClinPred

0.90

GERP RS

1.8

Varity_R

0.25

gMVP

0.22

Mutation Taster

=93/7

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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19-49054542-G-A

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