Genetic Variant NM_033183.3:c.200G>A (chr19-49047953-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033183.3(CGB8):c.200G>A(p.Gly67Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G67A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB8
NM_033183.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.158

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049676776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033183.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB8	NM_033183.3	MANE Select	c.200G>A	p.Gly67Glu	missense	Exon 3 of 3	NP_149439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGB8	ENST00000448456.4	TSL:1 MANE Select	c.200G>A	p.Gly67Glu	missense	Exon 3 of 3	ENSP00000403649.2	P0DN86-1
	CGB8	ENST00000933082.1		c.32G>A	p.Gly11Glu	missense	Exon 2 of 2	ENSP00000603141.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000185

AC:

AN:

54184

AF XY:

0.0000367

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.14e-7

AC:

AN:

1401048

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

696140

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31118

American (AMR)

AF:

0.00

AC:

AN:

43138

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24400

East Asian (EAS)

AF:

0.00

AC:

AN:

39250

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82532

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38510

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4028

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079888

Other (OTH)

AF:

0.00

AC:

AN:

58184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.71

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.48

M_CAP

Benign

0.038

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.64

PhyloP100

0.16

PrimateAI

Uncertain

0.71

PROVEAN

Benign

0.24

REVEL

Benign

0.26

Sift

Benign

0.34

Sift4G

Benign

1.0

Vest4

0.060

MutPred

0.28

Gain of solvent accessibility (P = 0.0281)

MVP

0.19

MPC

0.0071

ClinPred

0.37

GERP RS

-2.1

gMVP

0.067

Mutation Taster

=94/6

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over