Genetic Variant CGB7:p.Pro145Thr (chr19-49054356-G-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001385261.1(CGB7):c.433C>A(p.Pro145Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000444 in 150,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P145A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 22)

Exomes 𝑓: 0.000058 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB7
NM_001385261.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.671

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007793784).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB7	NM_001385261.1 link	c.433C>A	p.Pro145Thr	missense_variant	Exon 5 of 5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2 link	c.433C>A	p.Pro145Thr	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.433C>A	p.Pro145Thr	missense_variant	Exon 5 of 5		NM_001385261.1	ENSP00000507822.1	P0DN87
CGB7	ENST00000596965.5 link	c.433C>A	p.Pro145Thr	missense_variant	Exon 5 of 5	2		ENSP00000469076.1	P0DN87
CGB7	ENST00000597853.5 link	c.433C>A	p.Pro145Thr	missense_variant	Exon 5 of 5	2		ENSP00000470813.1	P0DN87

Frequencies

GnomAD3 genomes

AF:

0.000398

AC:

AN:

150794

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000664

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:

0.000100

AC:

AN:

228944

AF XY:

0.0000967

show subpopulations

Gnomad AFR exome

AF:

0.00136

Gnomad AMR exome

AF:

0.0000619

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000582

AC:

AN:

1459608

Hom.:

Cov.:

AF XY:

0.0000551

AC XY:

AN XY:

726080

show subpopulations

African (AFR)

AF:

0.00165

AC:

AN:

33406

American (AMR)

AF:

0.000134

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86090

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4196

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111764

Other (OTH)

AF:

0.000332

AC:

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000444

AC:

AN:

150910

Hom.:

Cov.:

AF XY:

0.000503

AC XY:

AN XY:

73598

show subpopulations

African (AFR)

AF:

0.00160

AC:

AN:

41290

American (AMR)

AF:

0.0000663

AC:

AN:

15088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5102

South Asian (SAS)

AF:

0.00

AC:

AN:

4690

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10456

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67540

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ESP6500AA

AF:

0.00233

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000141

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

T;T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.82

T;.;.

M_CAP

Benign

0.0016

MetaRNN

Benign

0.0078

T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.67

PROVEAN

Benign

-1.0

N;.;.

REVEL

Benign

0.035

Sift

Benign

0.13

T;.;.

Sift4G

Pathogenic

0.0

D;D;D

Vest4

0.28

MVP

0.10

MPC

2.3

ClinPred

0.018

GERP RS

0.47

Varity_R

0.098

gMVP

0.14

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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19-49054356-G-T

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