19-49035617-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_033377.2(CGB1):​c.461G>A​(p.Gly154Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,611,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 27)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CGB1
NM_033377.2 missense

Scores

16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.124
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0383375).
BP6
Variant 19-49035617-C-T is Benign according to our data. Variant chr19-49035617-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3832620.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CGB1NM_033377.2 linkc.461G>A p.Gly154Glu missense_variant Exon 3 of 3 ENST00000301407.8 NP_203695.2 A6NKQ9-2
CGB1NM_001382421.1 linkc.425G>A p.Gly142Glu missense_variant Exon 3 of 3 NP_001369350.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CGB1ENST00000301407.8 linkc.461G>A p.Gly154Glu missense_variant Exon 3 of 3 1 NM_033377.2 ENSP00000301407.6 A6NKQ9-2
ENSG00000267335ENST00000591656.1 linkc.-28+909G>A intron_variant Intron 1 of 2 2 ENSP00000466140.1 K7ELM3
ENSG00000267335ENST00000604577.1 linkc.9+1086G>A intron_variant Intron 1 of 2 1 ENSP00000474022.1 S4R385
CGB1ENST00000601167.1 linkc.*36G>A downstream_gene_variant 5 ENSP00000472896.2 K7ELM3

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151620
Hom.:
0
Cov.:
27
show subpopulations
Gnomad AFR
AF:
0.0000244
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
250958
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.0000624
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000959
AC:
14
AN:
1459786
Hom.:
0
Cov.:
34
AF XY:
0.0000110
AC XY:
8
AN XY:
726192
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
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:
0.0000108
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151620
Hom.:
0
Cov.:
27
AF XY:
0.0000270
AC XY:
2
AN XY:
74056
show subpopulations
Gnomad4 AFR
AF:
0.0000244
Gnomad4 AMR
AF:
0.000131
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:
0.00
Bravo
AF:
0.0000264
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 25, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
0.54
DANN
Benign
0.46
Eigen
Benign
-2.1
Eigen_PC
Benign
-2.2
FATHMM_MKL
Benign
0.00010
N
LIST_S2
Benign
0.37
T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.038
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.37
T
PROVEAN
Benign
0.64
N
REVEL
Benign
0.052
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.14
Gain of solvent accessibility (P = 0.024);
MVP
0.030
MPC
1.5
ClinPred
0.053
T
GERP RS
-1.3
gMVP
0.028

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.

Other links and lift over

dbSNP: rs781171716; hg19: chr19-49538874; API