19-49033156-C-T

Position:

chr19-49033156-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033378.2(CGB2):c.427C>T(p.Pro143Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,610,668 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

CGB2
NM_033378.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.654

Variant links:

Genes affected

CGB2 (HGNC:16722): (chorionic gonadotropin subunit beta 2) The beta subunit of chorionic gonadotropin (CGB) is encoded by six highly homologous and structurally similar genes that are arranged in tandem and inverted pairs on chromosome 19q13.3, and contiguous with the luteinizing hormone beta (LHB) subunit gene. The CGB genes are primarily distinguished by differences in the 5' untranscribed region. This gene was originally thought to be one of the two pseudogenes (CGB1 and CGB2) of CGB subunit, however, detection of CGB1 and CGB2 transcripts in vivo, and their presence on the polysomes, suggested that these transcripts are translated. To date, a protein product corresponding to CGB2 has not been isolated. The deduced sequence of the hypothetical protein of 132 aa does not share any similarity with that of functional CGB subunits (PMID:8954017). However, a 163 aa protein, translated from a different frame, is about the same size, and shares 98% identity with other CGB subunits. [provided by RefSeq, Jul 2008]

CGB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16688189).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB2	NM_033378.2 linkuse as main transcript	c.427C>T	p.Pro143Ser	missense_variant	3/3	ENST00000359342.7	NP_203696.2
CGB2	NM_001319065.2 linkuse as main transcript	c.391C>T	p.Pro131Ser	missense_variant	3/3		NP_001305994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGB2	ENST00000359342.7 linkuse as main transcript	c.427C>T	p.Pro143Ser	missense_variant	3/3	1	NM_033378.2	ENSP00000352295	P1
CGB2	ENST00000474913.1 linkuse as main transcript			downstream_gene_variant		1		ENSP00000471177

Frequencies

GnomAD3 genomes

AF:

0.0000265

AC:

AN:

150938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250166

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1459612

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.0000117

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000265

AC:

AN:

151056

Hom.:

Cov.:

AF XY:

0.0000542

AC XY:

AN XY:

73860

show subpopulations

Gnomad4 AFR

AF:

0.0000246

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

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

Sep 29, 2023

The c.427C>T (p.P143S) alteration is located in exon 3 (coding exon 3) of the CGB2 gene. This alteration results from a C to T substitution at nucleotide position 427, causing the proline (P) at amino acid position 143 to be replaced by a serine (S). 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

0.079

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.84

M_CAP

Benign

0.0027

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.91

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.95

REVEL

Benign

0.11

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0

Vest4

0.32

MVP

0.42

MPC

3.1

ClinPred

0.19

GERP RS

0.043

Varity_R

0.057

gMVP

0.14

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