19-49054462-T-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001385261.1(CGB7):​c.327A>C​(p.Gln109His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q109L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 20)
Exomes 𝑓: 0.0000090 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CGB7
NM_001385261.1 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.719

Publications

0 publications found
Variant links:
Genes affected
CGB7 (HGNC:16451): (chorionic gonadotropin subunit beta 7) This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 7 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]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03092575).
BP6
Variant 19-49054462-T-G is Benign according to our data. Variant chr19-49054462-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3491738.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CGB7NM_001385261.1 linkc.327A>C p.Gln109His missense_variant Exon 5 of 5 ENST00000684222.1 NP_001372190.1
CGB7NM_033142.2 linkc.327A>C p.Gln109His missense_variant Exon 5 of 5 NP_149133.1 P0DN87A0A0F7RQF0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CGB7ENST00000684222.1 linkc.327A>C p.Gln109His missense_variant Exon 5 of 5 NM_001385261.1 ENSP00000507822.1 P0DN87
CGB7ENST00000596965.5 linkc.327A>C p.Gln109His missense_variant Exon 5 of 5 2 ENSP00000469076.1 P0DN87
CGB7ENST00000597853.5 linkc.327A>C p.Gln109His missense_variant Exon 5 of 5 2 ENSP00000470813.1 P0DN87

Frequencies

GnomAD3 genomes
AF:
0.0000140
AC:
2
AN:
142388
Hom.:
0
Cov.:
20
show subpopulations
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:
0.0000310
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
91566
AF XY:
0.00
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000899
AC:
13
AN:
1445388
Hom.:
0
Cov.:
34
AF XY:
0.0000111
AC XY:
8
AN XY:
718408
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33278
American (AMR)
AF:
0.00
AC:
0
AN:
43944
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25756
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39502
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85214
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52790
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4108
European-Non Finnish (NFE)
AF:
0.0000118
AC:
13
AN:
1101154
Other (OTH)
AF:
0.00
AC:
0
AN:
59642
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.490
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000140
AC:
2
AN:
142388
Hom.:
0
Cov.:
20
AF XY:
0.00
AC XY:
0
AN XY:
68628
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
38946
American (AMR)
AF:
0.00
AC:
0
AN:
14048
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3372
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4782
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4080
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
9492
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
308
European-Non Finnish (NFE)
AF:
0.0000310
AC:
2
AN:
64588
Other (OTH)
AF:
0.00
AC:
0
AN:
1892
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Benign:1
Dec 06, 2024
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
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
2.7
DANN
Benign
0.10
DEOGEN2
Benign
0.26
T;T;T
Eigen
Benign
-1.8
Eigen_PC
Benign
-1.8
FATHMM_MKL
Benign
0.0067
N
LIST_S2
Benign
0.034
T;.;.
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.031
T;T;T
MetaSVM
Benign
-1.0
T
PhyloP100
0.72
PROVEAN
Benign
1.9
N;.;.
REVEL
Benign
0.040
Sift
Benign
1.0
T;.;.
Sift4G
Benign
1.0
T;T;T
Vest4
0.10
MVP
0.040
MPC
0.96
ClinPred
0.059
T
GERP RS
-2.9
Varity_R
0.045
gMVP
0.11
Mutation Taster
=91/9
polymorphism

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

Other links and lift over

dbSNP: rs780960921; hg19: chr19-49557719; API