chr1-156381908-G-A

Variant summary

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

The NM_020407.5(RHBG):​c.943G>A​(p.Gly315Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.45 in 1,609,256 control chromosomes in the GnomAD database, including 165,875 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 0.48 ( 18171 hom., cov: 31)
Exomes 𝑓: 0.45 ( 147704 hom. )

Consequence

RHBG
NM_020407.5 missense

Scores

5
4
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.76

Publications

28 publications found
Variant links:
Genes affected
RHBG (HGNC:14572): (Rh family B glycoprotein) This gene encodes one of two non-erythroid members of the Rhesus (Rh) protein family. Non-erythroid Rh protein family members are mainly expressed in the kidney and belong to the methylammonium-ammonium permease/ammonia transporters superfamily. All Rh family proteins are predicted to be transmembrane proteins with 12 membrane spanning domains and intracytoplasmic N- and C-termini. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

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=3.0048128E-5).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RHBGNM_020407.5 linkc.943G>A p.Gly315Arg missense_variant Exon 6 of 10 ENST00000537040.6 NP_065140.3 Q9H310-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RHBGENST00000537040.6 linkc.943G>A p.Gly315Arg missense_variant Exon 6 of 10 1 NM_020407.5 ENSP00000441197.2 Q9H310-1

Frequencies

GnomAD3 genomes
AF:
0.484
AC:
73532
AN:
151772
Hom.:
18168
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.540
Gnomad AMI
AF:
0.550
Gnomad AMR
AF:
0.549
Gnomad ASJ
AF:
0.437
Gnomad EAS
AF:
0.697
Gnomad SAS
AF:
0.445
Gnomad FIN
AF:
0.428
Gnomad MID
AF:
0.465
Gnomad NFE
AF:
0.434
Gnomad OTH
AF:
0.476
GnomAD2 exomes
AF:
0.481
AC:
117936
AN:
244952
AF XY:
0.470
show subpopulations
Gnomad AFR exome
AF:
0.547
Gnomad AMR exome
AF:
0.610
Gnomad ASJ exome
AF:
0.427
Gnomad EAS exome
AF:
0.707
Gnomad FIN exome
AF:
0.427
Gnomad NFE exome
AF:
0.428
Gnomad OTH exome
AF:
0.466
GnomAD4 exome
AF:
0.446
AC:
650189
AN:
1457366
Hom.:
147704
Cov.:
50
AF XY:
0.445
AC XY:
322676
AN XY:
725250
show subpopulations
African (AFR)
AF:
0.545
AC:
18045
AN:
33086
American (AMR)
AF:
0.604
AC:
25719
AN:
42608
Ashkenazi Jewish (ASJ)
AF:
0.433
AC:
11210
AN:
25900
East Asian (EAS)
AF:
0.698
AC:
27694
AN:
39680
South Asian (SAS)
AF:
0.443
AC:
37998
AN:
85766
European-Finnish (FIN)
AF:
0.429
AC:
22922
AN:
53386
Middle Eastern (MID)
AF:
0.443
AC:
2551
AN:
5754
European-Non Finnish (NFE)
AF:
0.429
AC:
476687
AN:
1110984
Other (OTH)
AF:
0.455
AC:
27363
AN:
60202
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.478
Heterozygous variant carriers
0
20212
40424
60636
80848
101060
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
14746
29492
44238
58984
73730
<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:
0.484
AC:
73562
AN:
151890
Hom.:
18171
Cov.:
31
AF XY:
0.483
AC XY:
35821
AN XY:
74212
show subpopulations
African (AFR)
AF:
0.540
AC:
22356
AN:
41426
American (AMR)
AF:
0.549
AC:
8371
AN:
15254
Ashkenazi Jewish (ASJ)
AF:
0.437
AC:
1518
AN:
3472
East Asian (EAS)
AF:
0.698
AC:
3594
AN:
5152
South Asian (SAS)
AF:
0.443
AC:
2133
AN:
4810
European-Finnish (FIN)
AF:
0.428
AC:
4512
AN:
10534
Middle Eastern (MID)
AF:
0.452
AC:
131
AN:
290
European-Non Finnish (NFE)
AF:
0.434
AC:
29460
AN:
67942
Other (OTH)
AF:
0.470
AC:
988
AN:
2102
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1888
3776
5664
7552
9440
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
658
1316
1974
2632
3290
<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:
0.451
Hom.:
46239
Bravo
AF:
0.498
TwinsUK
AF:
0.407
AC:
1509
ALSPAC
AF:
0.430
AC:
1657
ESP6500AA
AF:
0.526
AC:
2175
ESP6500EA
AF:
0.425
AC:
3575
ExAC
AF:
0.479
AC:
57993
Asia WGS
AF:
0.521
AC:
1813
AN:
3478
EpiCase
AF:
0.425
EpiControl
AF:
0.425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Pathogenic
0.26
CADD
Pathogenic
32
DANN
Pathogenic
1.0
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Uncertain
0.96
D
MetaRNN
Benign
0.000030
T
MetaSVM
Uncertain
-0.25
T
PhyloP100
7.8
PrimateAI
Uncertain
0.67
T
REVEL
Uncertain
0.56
Sift4G
Pathogenic
0.0010
D
Vest4
0.33
MutPred
0.91
Gain of methylation at G315 (P = 0.0123);
ClinPred
0.059
T
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
gMVP
0.98
Mutation Taster
=61/39
polymorphism (auto)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs3748569; hg19: chr1-156351699; COSMIC: COSV54804391; COSMIC: COSV54804391; API