Genetic Variant NM_033183.3:c.145G>A (chr19-49048243-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_033183.3(CGB8):c.145G>A(p.Val49Ile) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0082 ( 3 hom., cov: 26)

Exomes 𝑓: 0.010 ( 40 hom. )

Failed GnomAD Quality Control

Consequence

CGB8
NM_033183.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.763

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008599371).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CGB8	NM_033183.3 link	c.145G>A	p.Val49Ile	missense_variant	Exon 2 of 3	ENST00000448456.4	NP_149439.1	P0DN86-1A0A0F7RQP8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CGB8	ENST00000448456.4 link	c.145G>A	p.Val49Ile	missense_variant	Exon 2 of 3	1	NM_033183.3	ENSP00000403649.2		P0DN86-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1212

AN:

147796

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.000199

Gnomad SAS

AF:

0.00169

Gnomad FIN

AF:

0.0102

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0118

Gnomad OTH

AF:

0.00687

GnomAD3 exomes

AF:

0.00803

AC:

431

AN:

53646

Hom.:

AF XY:

0.00757

AC XY:

205

AN XY:

27066

show subpopulations

Gnomad AFR exome

AF:

0.00269

Gnomad AMR exome

AF:

0.0108

Gnomad ASJ exome

AF:

0.00616

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00165

Gnomad FIN exome

AF:

0.0129

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.0100

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0102

AC:

14383

AN:

1403336

Hom.:

Cov.:

AF XY:

0.00994

AC XY:

6922

AN XY:

696332

show subpopulations

Gnomad4 AFR exome

AF:

0.00188

Gnomad4 AMR exome

AF:

0.00713

Gnomad4 ASJ exome

AF:

0.00422

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.00214

Gnomad4 FIN exome

AF:

0.0111

Gnomad4 NFE exome

AF:

0.0117

Gnomad4 OTH exome

AF:

0.00978

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00819

AC:

1211

AN:

147912

Hom.:

Cov.:

AF XY:

0.00835

AC XY:

602

AN XY:

72124

show subpopulations

Gnomad4 AFR

AF:

0.00224

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.00462

Gnomad4 EAS

AF:

0.000199

Gnomad4 SAS

AF:

0.00169

Gnomad4 FIN

AF:

0.0102

Gnomad4 NFE

AF:

0.0118

Gnomad4 OTH

AF:

0.00680

Alfa

AF:

0.00632

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

8.8

DANN

Benign

0.96

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.85

M_CAP

Benign

0.0085

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.74

PROVEAN

Benign

0.32

REVEL

Benign

0.029

Sift

Benign

0.42

Sift4G

Benign

0.73

Vest4

0.13

MVP

0.14

MPC

0.015

ClinPred

0.016

GERP RS

0.71

gMVP

0.029

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over