Variant 19-49035893-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_033377.2(CGB1):c.185T>G(p.Val62Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000169 in 1,227,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CGB1
NM_033377.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.19

Variant links:

Genes affected

CGB1 (HGNC:16721): (chorionic gonadotropin subunit beta 1) 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 CGB1 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 155 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]

CGB1 links:

ENSG00000267335 (HGNC:):

ENSG00000267335 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGB1	NM_033377.2 link	c.185T>G	p.Val62Gly	missense_variant	3/3	ENST00000301407.8	NP_203695.2	A6NKQ9-2
CGB1	NM_001382421.1 link	c.149T>G	p.Val50Gly	missense_variant	3/3		NP_001369350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CGB1	ENST00000301407.8 link	c.185T>G	p.Val62Gly	missense_variant	3/3	1	NM_033377.2	ENSP00000301407.6	A6NKQ9-2
ENSG00000267335	ENST00000591656.1 link	c.-28+633T>G		intron_variant		2		ENSP00000466140.1	K7ELM3
ENSG00000267335	ENST00000604577.1 link	c.9+810T>G		intron_variant		1		ENSP00000474022.1	S4R385
CGB1	ENST00000601167.1 link	c.149T>G	p.Val50Gly	missense_variant	3/3	5		ENSP00000472896.2	K7ELM3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

145754

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:

0.0000602

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000169

AC:

208

AN:

1227834

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

106

AN XY:

605980

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:

0.000217

Gnomad4 OTH exome

AF:

0.0000385

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000274

AC:

AN:

145754

Hom.:

Cov.:

AF XY:

0.0000424

AC XY:

AN XY:

70832

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:

0.0000602

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

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

Apr 25, 2023

The c.185T>G (p.V62G) alteration is located in exon 3 (coding exon 3) of the CGB1 gene. This alteration results from a T to G substitution at nucleotide position 185, causing the valine (V) at amino acid position 62 to be replaced by a glycine (G). 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

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.15

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Benign

0.0042

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.63

T;T

M_CAP

Pathogenic

0.30

MetaRNN

Pathogenic

0.86

D;D

MetaSVM

Uncertain

0.69

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-6.2

D;.

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;.

Sift4G

Uncertain

0.0040

D;.

Polyphen

1.0

D;.

Vest4

0.55

MutPred

0.68

Loss of stability (P = 0.0078);.;

MVP

0.70

MPC

2.7

ClinPred

0.97

GERP RS

1.8

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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