rs6076347

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.71

Publications

54 publications found

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]

GINS1 Gene-Disease associations (from GenCC):

combined immunodeficiency due to GINS1 deficiency
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

GINS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
GINS1	NM_021067.5 link	c.289G>A	p.Val97Ile	missense_variant	Exon 4 of 7	ENST00000262460.5	NP_066545.3	Q14691

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GINS1	ENST00000262460.5 link	c.289G>A	p.Val97Ile	missense_variant	Exon 4 of 7	1	NM_021067.5	ENSP00000262460.4		Q14691

Frequencies

GnomAD3 genomes

AF:

0.350

AC:

53136

AN:

151968

Hom.:

10898

Cov.:

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

GnomAD2 exomes

AF:

0.382

AC:

95925

AN:

251376

AF XY:

0.389

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 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.:

AF XY:

0.437

AC XY:

315149

AN XY:

720662

show subpopulations

African (AFR)

AF:

0.142

AC:

4716

AN:

33298

American (AMR)

AF:

0.388

AC:

17364

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

12777

AN:

26040

East Asian (EAS)

AF:

0.00328

AC:

130

AN:

39676

South Asian (SAS)

AF:

0.328

AC:

28205

AN:

85972

European-Finnish (FIN)

AF:

0.425

AC:

22680

AN:

53354

Middle Eastern (MID)

AF:

0.450

AC:

2582

AN:

5734

European-Non Finnish (NFE)

AF:

0.475

AC:

521339

AN:

1098022

Other (OTH)

AF:

0.413

AC:

24715

AN:

59894

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

15524

31049

46573

62098

77622

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14966

29932

44898

59864

74830

<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:

0.349

AC:

53147

AN:

152086

Hom.:

10903

Cov.:

AF XY:

0.345

AC XY:

25626

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.154

AC:

6388

AN:

41484

American (AMR)

AF:

0.382

AC:

5827

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

1681

AN:

3472

East Asian (EAS)

AF:

0.00887

AC:

AN:

5188

South Asian (SAS)

AF:

0.313

AC:

1507

AN:

4820

European-Finnish (FIN)

AF:

0.424

AC:

4472

AN:

10556

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.471

AC:

32001

AN:

67980

Other (OTH)

AF:

0.384

AC:

810

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1612

3224

4836

6448

8060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.433

Hom.:

74132

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 13, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This 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

Aug 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.3

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.086

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.85

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.75

MetaRNN

Benign

0.00082

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.77

PhyloP100

1.7

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.23

REVEL

Benign

0.054

Sift

Benign

1.0

Sift4G

Benign

0.94

Polyphen

0.0020

Vest4

0.056

MPC

0.21

ClinPred

0.0013

GERP RS

0.27

Varity_R

0.049

gMVP

0.39

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over