19-49054455-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001385261.1(CGB7):​c.334C>T​(p.Leu112Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000076 ( 0 hom., cov: 20)
Exomes 𝑓: 0.00018 ( 2 hom. )
Failed GnomAD Quality Control

Consequence

CGB7
NM_001385261.1 missense

Scores

6
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42
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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.035449624).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CGB7NM_001385261.1 linkuse as main transcriptc.334C>T p.Leu112Phe missense_variant 5/5 ENST00000684222.1 NP_001372190.1
CGB7NM_033142.2 linkuse as main transcriptc.334C>T p.Leu112Phe missense_variant 5/5 NP_149133.1 P0DN87A0A0F7RQF0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CGB7ENST00000684222.1 linkuse as main transcriptc.334C>T p.Leu112Phe missense_variant 5/5 NM_001385261.1 ENSP00000507822.1 P0DN87
CGB7ENST00000596965.5 linkuse as main transcriptc.334C>T p.Leu112Phe missense_variant 5/52 ENSP00000469076.1 P0DN87
CGB7ENST00000597853.5 linkuse as main transcriptc.334C>T p.Leu112Phe missense_variant 5/52 ENSP00000470813.1 P0DN87

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
11
AN:
144954
Hom.:
0
Cov.:
20
FAILED QC
Gnomad AFR
AF:
0.000177
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000938
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000307
AC:
29
AN:
94548
Hom.:
0
AF XY:
0.000348
AC XY:
17
AN XY:
48882
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 SAS exome
AF:
0.00263
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000276
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000176
AC:
255
AN:
1447154
Hom.:
2
Cov.:
34
AF XY:
0.000250
AC XY:
180
AN XY:
719414
show subpopulations
Gnomad4 AFR exome
AF:
0.000210
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00275
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000363
Gnomad4 OTH exome
AF:
0.000168
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000758
AC:
11
AN:
145072
Hom.:
0
Cov.:
20
AF XY:
0.0000997
AC XY:
7
AN XY:
70234
show subpopulations
Gnomad4 AFR
AF:
0.000176
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000939
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.000149
AC:
14

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 submitterclinical testingAmbry GeneticsJul 06, 2021The c.334C>T (p.L112F) alteration is located in exon 3 (coding exon 3) of the CGB7 gene. This alteration results from a C to T substitution at nucleotide position 334, causing the leucine (L) at amino acid position 112 to be replaced by a phenylalanine (F). 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
0.14
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
16
DANN
Benign
0.96
DEOGEN2
Uncertain
0.64
D;D;D
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.52
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.88
D;.;.
M_CAP
Benign
0.071
D
MetaRNN
Benign
0.035
T;T;T
MetaSVM
Uncertain
-0.099
T
PROVEAN
Uncertain
-2.6
D;.;.
REVEL
Uncertain
0.34
Sift
Benign
0.45
T;.;.
Sift4G
Benign
0.13
T;T;T
Vest4
0.16
MVP
0.62
MPC
1.9
ClinPred
0.094
T
GERP RS
0.67
Varity_R
0.13
gMVP
0.034

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs751967082; hg19: chr19-49557712; COSMIC: COSV105907177; COSMIC: COSV105907177; API