Variant 19-49054505-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001385261.1(CGB7):c.284G>A(p.Gly95Asp) 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.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 19)

Exomes 𝑓: 0.0000072 ( 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: 3.53

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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.947

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB7	NM_001385261.1 linkuse as main transcript	c.284G>A	p.Gly95Asp	missense_variant	5/5	ENST00000684222.1	NP_001372190.1
CGB7	NM_033142.2 linkuse as main transcript	c.284G>A	p.Gly95Asp	missense_variant	5/5		NP_149133.1	P0DN87A0A0F7RQF0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CGB7	ENST00000684222.1 linkuse as main transcript	c.284G>A	p.Gly95Asp	missense_variant	5/5		NM_001385261.1	ENSP00000507822.1	P0DN87
CGB7	ENST00000596965.5 linkuse as main transcript	c.284G>A	p.Gly95Asp	missense_variant	5/5	2		ENSP00000469076.1	P0DN87
CGB7	ENST00000597853.5 linkuse as main transcript	c.284G>A	p.Gly95Asp	missense_variant	5/5	2		ENSP00000470813.1	P0DN87

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

135858

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000427

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

GnomAD3 exomes

AF:

0.0000586

AC:

AN:

68246

Hom.:

AF XY:

0.0000287

AC XY:

AN XY:

34866

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.00000722

AC:

AN:

1384518

Hom.:

Cov.:

AF XY:

0.00000436

AC XY:

AN XY:

687480

show subpopulations

Gnomad4 AFR exome

AF:

0.000276

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000174

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000118

AC:

AN:

135858

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

65008

show subpopulations

Gnomad4 AFR

AF:

0.000427

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.284G>A (p.G95D) alteration is located in exon 3 (coding exon 3) of the CGB7 gene. This alteration results from a G to A substitution at nucleotide position 284, causing the glycine (G) at amino acid position 95 to be replaced by an aspartic acid (D). 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

Benign

0.15

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.66

D;D;D

Eigen

Benign

0.17

Eigen_PC

Benign

0.0060

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

T;.;.

M_CAP

Pathogenic

0.37

MetaRNN

Pathogenic

0.95

D;D;D

MetaSVM

Pathogenic

0.81

PROVEAN

Pathogenic

-6.0

D;.;.

REVEL

Pathogenic

0.69

Sift

Uncertain

0.014

D;.;.

Sift4G

Benign

0.20

T;T;T

Vest4

0.70

MVP

0.82

MPC

2.5

ClinPred

0.32

GERP RS

1.8

Varity_R

0.54

gMVP

0.11

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over