Variant chr19-49047779-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033183.3(CGB8):c.374A>T(p.Asp125Val) 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 24)

Exomes 𝑓: 0.0000071 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB8
NM_033183.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.656

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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.069155216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CGB8	NM_033183.3 linkuse as main transcript	c.374A>T	p.Asp125Val	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.374A>T	p.Asp125Val	missense_variant	3/3	1	NM_033183.3	P1	P0DN86-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

149610

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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:

0.000486

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

55452

Hom.:

AF XY:

0.00

AC XY:

AN XY:

28028

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000470

Gnomad OTH exome

AF:

0.000519

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000714

AC:

AN:

1260402

Hom.:

Cov.:

AF XY:

0.00000640

AC XY:

AN XY:

625430

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000209

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000267

AC:

AN:

149728

Hom.:

Cov.:

AF XY:

0.0000274

AC XY:

AN XY:

73096

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.00192

Bravo

AF:

0.00000378

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

Oct 10, 2023

The c.374A>T (p.D125V) alteration is located in exon 3 (coding exon 3) of the CGB8 gene. This alteration results from a A to T substitution at nucleotide position 374, causing the aspartic acid (D) at amino acid position 125 to be replaced by a valine (V). 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

0.24

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.84

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.0093

MetaRNN

Benign

0.069

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

2.2

REVEL

Benign

0.12

Sift

Benign

0.33

Sift4G

Benign

0.30

Vest4

0.15

MutPred

0.39

Loss of solvent accessibility (P = 0.0159);

MVP

0.31

MPC

0.0082

ClinPred

0.051

GERP RS

-3.6

gMVP

0.033

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