chr7-1093535-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001098201.3(GPER1):​c.*679G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 470,740 control chromosomes in the GnomAD database, including 8,508 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 4318 hom., cov: 33)
Exomes 𝑓: 0.15 ( 4190 hom. )

Consequence

GPER1
NM_001098201.3 3_prime_UTR

Scores

10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.08

Publications

13 publications found
Variant links:
Genes affected
GPER1 (HGNC:4485): (G protein-coupled estrogen receptor 1) This gene encodes a multi-pass membrane protein that localizes to the endoplasmic reticulum and a member of the G-protein coupled receptor 1 family. This receptor binds estrogen and activates multiple downstream signaling pathways, leading to stimulation of adenylate cyclase and an increase in cyclic AMP levels, while also promoting intracellular calcium mobilization and synthesis of phosphatidylinositol 3,4,5-trisphosphate in the nucleus. This protein therefore plays a role in the rapid nongenomic signaling events widely observed following stimulation of cells and tissues with estrogen. This receptor has been shown to play a role in diverse biological processes, including bone and nervous system development, metabolism, cognition, male fertility and uterine function. [provided by RefSeq, Aug 2017]
CHLSN (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0024252534).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPER1NM_001098201.3 linkc.*679G>T 3_prime_UTR_variant Exon 2 of 2 ENST00000397088.4 NP_001091671.1 Q99527A0A024R849
CHLSNNM_001318252.2 linkc.129+33722C>A intron_variant Intron 2 of 4 ENST00000397098.8 NP_001305181.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPER1ENST00000397088.4 linkc.*679G>T 3_prime_UTR_variant Exon 2 of 2 1 NM_001098201.3 ENSP00000380277.3 Q99527
C7orf50ENST00000397098.8 linkc.129+33722C>A intron_variant Intron 2 of 4 1 NM_001318252.2 ENSP00000380286.3 Q9BRJ6

Frequencies

GnomAD3 genomes
AF:
0.211
AC:
32088
AN:
151998
Hom.:
4309
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.385
Gnomad AMI
AF:
0.166
Gnomad AMR
AF:
0.157
Gnomad ASJ
AF:
0.172
Gnomad EAS
AF:
0.0780
Gnomad SAS
AF:
0.148
Gnomad FIN
AF:
0.113
Gnomad MID
AF:
0.159
Gnomad NFE
AF:
0.151
Gnomad OTH
AF:
0.205
GnomAD2 exomes
AF:
0.149
AC:
22478
AN:
151050
AF XY:
0.149
show subpopulations
Gnomad AFR exome
AF:
0.395
Gnomad AMR exome
AF:
0.119
Gnomad ASJ exome
AF:
0.173
Gnomad EAS exome
AF:
0.0677
Gnomad FIN exome
AF:
0.117
Gnomad NFE exome
AF:
0.150
Gnomad OTH exome
AF:
0.150
GnomAD4 exome
AF:
0.152
AC:
48315
AN:
318624
Hom.:
4190
Cov.:
0
AF XY:
0.153
AC XY:
27522
AN XY:
180000
show subpopulations
African (AFR)
AF:
0.393
AC:
3393
AN:
8632
American (AMR)
AF:
0.119
AC:
3259
AN:
27286
Ashkenazi Jewish (ASJ)
AF:
0.171
AC:
1842
AN:
10790
East Asian (EAS)
AF:
0.0686
AC:
632
AN:
9214
South Asian (SAS)
AF:
0.156
AC:
9326
AN:
59742
European-Finnish (FIN)
AF:
0.116
AC:
3109
AN:
26834
Middle Eastern (MID)
AF:
0.118
AC:
328
AN:
2776
European-Non Finnish (NFE)
AF:
0.151
AC:
24068
AN:
159028
Other (OTH)
AF:
0.165
AC:
2358
AN:
14322
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.491
Heterozygous variant carriers
0
2900
5800
8701
11601
14501
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
184
368
552
736
920
<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:
0.211
AC:
32129
AN:
152116
Hom.:
4318
Cov.:
33
AF XY:
0.206
AC XY:
15359
AN XY:
74380
show subpopulations
African (AFR)
AF:
0.385
AC:
15949
AN:
41474
American (AMR)
AF:
0.157
AC:
2402
AN:
15276
Ashkenazi Jewish (ASJ)
AF:
0.172
AC:
596
AN:
3464
East Asian (EAS)
AF:
0.0778
AC:
402
AN:
5166
South Asian (SAS)
AF:
0.148
AC:
712
AN:
4822
European-Finnish (FIN)
AF:
0.113
AC:
1192
AN:
10594
Middle Eastern (MID)
AF:
0.154
AC:
45
AN:
292
European-Non Finnish (NFE)
AF:
0.151
AC:
10244
AN:
68000
Other (OTH)
AF:
0.206
AC:
436
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1227
2454
3680
4907
6134
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
326
652
978
1304
1630
<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:
0.152
Hom.:
1661
Bravo
AF:
0.220
TwinsUK
AF:
0.149
AC:
552
ALSPAC
AF:
0.160
AC:
617
ExAC
AF:
0.146
AC:
2886
Asia WGS
AF:
0.148
AC:
514
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.87
T
BayesDel_noAF
Benign
-0.87
CADD
Benign
0.38
DANN
Benign
0.58
Eigen
Benign
-0.93
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.068
N
LIST_S2
Benign
0.30
T
MetaRNN
Benign
0.0024
T
MetaSVM
Benign
-0.97
T
PhyloP100
-2.1
Vest4
0.13
ClinPred
0.0033
T
GERP RS
-3.1
Mutation Taster
=100/0
polymorphism (auto)

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: rs3808354; hg19: chr7-1133171; COSMIC: COSV52467725; COSMIC: COSV52467725; API