Variant 19-49023530-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_000737.5(CGB3):c.89G>A(p.Arg30His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 9)

Exomes 𝑓: 0.00053 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB3
NM_000737.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0120

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 made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35607034).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB3	NM_000737.5 linkuse as main transcript	c.89G>A	p.Arg30His	missense_variant	2/3	ENST00000357383.4	NP_000728.1	P0DN86-1A0A0F7RQP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CGB3	ENST00000357383.4 linkuse as main transcript	c.89G>A	p.Arg30His	missense_variant	2/3	1	NM_000737.5	ENSP00000349954.2	P0DN86-1
ENSG00000267335	ENST00000591656.1 linkuse as main transcript	c.47G>A	p.Arg16His	missense_variant	2/3	2		ENSP00000466140.1	K7ELM3
ENSG00000267335	ENST00000604577.1 linkuse as main transcript	c.83G>A	p.Arg28His	missense_variant	2/3	1		ENSP00000474022.1	S4R385

Frequencies

GnomAD3 genomes

AF:

0.000757

AC:

AN:

71348

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000178

Gnomad ASJ

AF:

0.000494

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000527

Gnomad FIN

AF:

0.000235

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000312

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000533

AC:

264

AN:

494926

Hom.:

Cov.:

AF XY:

0.000553

AC XY:

142

AN XY:

256822

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.000273

Gnomad4 ASJ exome

AF:

0.000292

Gnomad4 EAS exome

AF:

0.0000648

Gnomad4 SAS exome

AF:

0.000490

Gnomad4 FIN exome

AF:

0.000429

Gnomad4 NFE exome

AF:

0.000590

Gnomad4 OTH exome

AF:

0.000478

GnomAD4 genome

AF:

0.000756

AC:

AN:

71402

Hom.:

Cov.:

AF XY:

0.000734

AC XY:

AN XY:

32686

show subpopulations

Gnomad4 AFR

AF:

0.00191

Gnomad4 AMR

AF:

0.000178

Gnomad4 ASJ

AF:

0.000494

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000531

Gnomad4 FIN

AF:

0.000235

Gnomad4 NFE

AF:

0.000312

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00354

Hom.:

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

Aug 12, 2021

The c.89G>A (p.R30H) alteration is located in exon 2 (coding exon 2) of the CGB3 gene. This alteration results from a G to A substitution at nucleotide position 89, causing the arginine (R) at amino acid position 30 to be replaced by a histidine (H). 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

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.27

T;.;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.80

.;.;T

M_CAP

Benign

0.064

MetaRNN

Benign

0.36

T;T;T

MetaSVM

Benign

-0.36

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.23

N;.;.

REVEL

Benign

0.28

Sift

Benign

0.20

T;.;.

Sift4G

Benign

0.37

T;.;.

Vest4

0.096

MutPred

0.17

Loss of glycosylation at P27 (P = 0.08);.;.;

MVP

0.84

MPC

2.2

ClinPred

0.044

GERP RS

0.74

Varity_R

0.083

gMVP

0.095

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