19-49036261-C-T

Variant names:

Variant summary

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

The NM_033377.2(CGB1):c.52G>A(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,607,948 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00018 ( 0 hom., cov: 28)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

CGB1
NM_033377.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.593

Publications

1 publications found

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 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=0.011168808).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033377.2. 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
	CGB1	NM_033377.2	MANE Select	c.52G>A	p.Ala18Thr	missense	Exon 2 of 3	NP_203695.2	A6NKQ9-2
	CGB1	NM_001382421.1		c.16G>A	p.Ala6Thr	missense	Exon 2 of 3	NP_001369350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CGB1	ENST00000301407.8	TSL:1 MANE Select	c.52G>A	p.Ala18Thr	missense	Exon 2 of 3	ENSP00000301407.6	A6NKQ9-2
ENSG00000267335	ENST00000591656.1	TSL:2	c.-28+265G>A		intron	N/A	ENSP00000466140.1	K7ELM3
ENSG00000267335	ENST00000604577.1	TSL:1	c.9+442G>A		intron	N/A	ENSP00000474022.1	S4R385

Frequencies

GnomAD3 genomes

AF:

0.000185

AC:

AN:

151730

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.0000656

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000333

AC:

AN:

240402

AF XY:

0.0000152

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:

0.0000730

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000302

AC:

AN:

1456102

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

724504

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33410

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86156

European-Finnish (FIN)

AF:

0.0000201

AC:

AN:

49774

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4264

European-Non Finnish (NFE)

AF:

0.0000369

AC:

AN:

1111788

Other (OTH)

AF:

0.0000332

AC:

AN:

60176

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000210942), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.393

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

AF:

0.000184

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41324

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67916

Other (OTH)

AF:

0.00

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.434

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000839

Hom.:

ExAC

AF:

0.0000580

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.82

M_CAP

Benign

0.019

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.96

PhyloP100

0.59

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.3

REVEL

Benign

0.091

Sift

Benign

0.042

Sift4G

Uncertain

0.050

Polyphen

0.83

Vest4

0.26

MVP

0.32

MPC

1.6

ClinPred

0.62

GERP RS

1.8

gMVP

0.19

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over