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rs6076347

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_021067.5(GINS1):c.289G>A(p.Val97Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,598,772 control chromosomes in the GnomAD database, including 158,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. V97V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.35 ( 10903 hom., cov: 32)
Exomes 𝑓: 0.44 ( 147221 hom. )

Consequence

GINS1
NM_021067.5 missense

Scores

1
17

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.71
Variant links:
Genes affected
GINS1 (HGNC:28980): (GINS complex subunit 1) The yeast heterotetrameric GINS complex is made up of Sld5 (GINS4; MIM 610611), Psf1, Psf2 (GINS2; MIM 610609), and Psf3 (GINS3; MIM 610610). The formation of the GINS complex is essential for the initiation of DNA replication in yeast and Xenopus egg extracts (Ueno et al., 2005 [PubMed 16287864]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=8.201003E-4).
BP6
Variant 20-25418154-G-A is Benign according to our data. Variant chr20-25418154-G-A is described in ClinVar as [Benign]. Clinvar id is 1169882.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GINS1NM_021067.5 linkuse as main transcriptc.289G>A p.Val97Ile missense_variant 4/7 ENST00000262460.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GINS1ENST00000262460.5 linkuse as main transcriptc.289G>A p.Val97Ile missense_variant 4/71 NM_021067.5 P1

Frequencies

GnomAD3 genomes
AF:
0.350
AC:
53136
AN:
151968
Hom.:
10898
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.154
Gnomad AMI
AF:
0.335
Gnomad AMR
AF:
0.381
Gnomad ASJ
AF:
0.484
Gnomad EAS
AF:
0.00885
Gnomad SAS
AF:
0.312
Gnomad FIN
AF:
0.424
Gnomad MID
AF:
0.386
Gnomad NFE
AF:
0.471
Gnomad OTH
AF:
0.386
GnomAD3 exomes
AF:
0.382
AC:
95925
AN:
251376
Hom.:
20970
AF XY:
0.389
AC XY:
52875
AN XY:
135866
show subpopulations
Gnomad AFR exome
AF:
0.144
Gnomad AMR exome
AF:
0.386
Gnomad ASJ exome
AF:
0.487
Gnomad EAS exome
AF:
0.00500
Gnomad SAS exome
AF:
0.322
Gnomad FIN exome
AF:
0.425
Gnomad NFE exome
AF:
0.471
Gnomad OTH exome
AF:
0.426
GnomAD4 exome
AF:
0.439
AC:
634508
AN:
1446686
Hom.:
147221
Cov.:
28
AF XY:
0.437
AC XY:
315149
AN XY:
720662
show subpopulations
Gnomad4 AFR exome
AF:
0.142
Gnomad4 AMR exome
AF:
0.388
Gnomad4 ASJ exome
AF:
0.491
Gnomad4 EAS exome
AF:
0.00328
Gnomad4 SAS exome
AF:
0.328
Gnomad4 FIN exome
AF:
0.425
Gnomad4 NFE exome
AF:
0.475
Gnomad4 OTH exome
AF:
0.413
GnomAD4 genome
AF:
0.349
AC:
53147
AN:
152086
Hom.:
10903
Cov.:
32
AF XY:
0.345
AC XY:
25626
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.154
Gnomad4 AMR
AF:
0.382
Gnomad4 ASJ
AF:
0.484
Gnomad4 EAS
AF:
0.00887
Gnomad4 SAS
AF:
0.313
Gnomad4 FIN
AF:
0.424
Gnomad4 NFE
AF:
0.471
Gnomad4 OTH
AF:
0.384
Alfa
AF:
0.444
Hom.:
41242
Bravo
AF:
0.340
TwinsUK
AF:
0.478
AC:
1772
ALSPAC
AF:
0.485
AC:
1868
ESP6500AA
AF:
0.157
AC:
691
ESP6500EA
AF:
0.470
AC:
4039
ExAC
AF:
0.379
AC:
46020
Asia WGS
AF:
0.154
AC:
534
AN:
3478
EpiCase
AF:
0.483
EpiControl
AF:
0.486

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxOct 13, 2019- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingUnidad de Genómica Garrahan, Hospital de Pediatría GarrahanJan 24, 2024This variant is classified as Benign based on local population frequency. This variant was detected in 65% of patients studied by a panel of primary immunodeficiencies. Number of patients: 62. Only high quality variants are reported. -
Combined immunodeficiency due to GINS1 deficiency Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.073
BayesDel_addAF
Benign
-0.75
T
BayesDel_noAF
Benign
-0.70
Cadd
Benign
4.3
Dann
Benign
0.62
DEOGEN2
Benign
0.086
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.85
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.75
T
MetaRNN
Benign
0.00082
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.77
N
MutationTaster
Benign
0.047
P;P
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-0.23
N
REVEL
Benign
0.054
Sift
Benign
1.0
T
Sift4G
Benign
0.94
T
Polyphen
0.0020
B
Vest4
0.056
MPC
0.21
ClinPred
0.0013
T
GERP RS
0.27
Varity_R
0.049
gMVP
0.39

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: rs6076347; hg19: chr20-25398790; COSMIC: COSV52465262; COSMIC: COSV52465262; API