Variant 19-49047920-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_033183.3(CGB8):c.233A>C(p.Asn78Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB8
NM_033183.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.30

Variant links:

Genes affected

CGB8 (HGNC:16453): (chorionic gonadotropin subunit beta 8) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 8 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]

CGB8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061267257).

BP6

Variant 19-49047920-T-G is Benign according to our data. Variant chr19-49047920-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 2381382.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CGB8	NM_033183.3 linkuse as main transcript	c.233A>C	p.Asn78Thr	missense_variant	3/3	ENST00000448456.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CGB8	ENST00000448456.4 linkuse as main transcript	c.233A>C	p.Asn78Thr	missense_variant	3/3	1	NM_033183.3	P1	P0DN86-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

142456

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000165

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000210

Gnomad SAS

AF:

0.00115

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000122

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000112

AC:

AN:

53804

Hom.:

AF XY:

0.000111

AC XY:

AN XY:

27128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000993

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000191

AC:

207

AN:

1085694

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

132

AN XY:

549230

show subpopulations

Gnomad4 AFR exome

AF:

0.000199

Gnomad4 AMR exome

AF:

0.000194

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000787

Gnomad4 FIN exome

AF:

0.0000281

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.000189

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000154

AC:

AN:

142564

Hom.:

Cov.:

AF XY:

0.000173

AC XY:

AN XY:

69272

show subpopulations

Gnomad4 AFR

AF:

0.000165

Gnomad4 AMR

AF:

0.000136

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000210

Gnomad4 SAS

AF:

0.00115

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000122

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000123

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 25, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.30

CADD

Benign

5.4

DANN

Benign

0.65

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.54

M_CAP

Benign

0.065

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.77

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

2.9

REVEL

Benign

0.22

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.13

MVP

0.40

MPC

0.0056

ClinPred

0.026

GERP RS

0.69

gMVP

0.021

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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