rs300168

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001130009.3(GEN1):c.1971A>G(p.Glu657Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 1,612,856 control chromosomes in the GnomAD database, including 246,767 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 19084 hom., cov: 33)

Exomes 𝑓: 0.55 ( 227683 hom. )

Consequence

GEN1
NM_001130009.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.707

Publications

22 publications found

Variant links:

Genes affected

GEN1 (HGNC:26881): (GEN1 Holliday junction 5' flap endonuclease) This gene encodes a member of the Rad2/xeroderma pigmentosum group G nuclease family, whose members are characterized by N-terminal and internal xeroderma pigmentosum group G nuclease domains followed by helix-hairpin-helix domains and disordered C-terminal domains. The protein encoded by this gene is involved in resolution of Holliday junctions, which are intermediate four-way structures that covalently link DNA during homologous recombination and double-strand break repair. The protein resolves Holliday junctions by creating dual incisions across the junction to produce nicked duplex products that can be ligated. In addition, this protein has been found to localize to centrosomes where it has been implicated in regulation of centrosome integrity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

GEN1 links:

SMC6 (HGNC:20466): (structural maintenance of chromosomes 6) Enables ubiquitin protein ligase binding activity. Involved in several processes, including cellular senescence; positive regulation of chromosome segregation; and telomere maintenance via recombination. Located in chromosome and nuclear body. Part of Smc5-Smc6 complex. [provided by Alliance of Genome Resources, Apr 2022]

SMC6 links:

LOC105373449 (HGNC:):

LOC105373449 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 2-17781183-A-G is Benign according to our data. Variant chr2-17781183-A-G is described in ClinVar as Benign. ClinVar VariationId is 1169877.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.707 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130009.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GEN1	NM_001130009.3	MANE Select	c.1971A>G	p.Glu657Glu	synonymous	Exon 14 of 14	NP_001123481.3	Q17RS7
	GEN1	NM_182625.5		c.1971A>G	p.Glu657Glu	synonymous	Exon 14 of 14	NP_872431.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GEN1	ENST00000381254.7	TSL:5 MANE Select	c.1971A>G	p.Glu657Glu	synonymous	Exon 14 of 14	ENSP00000370653.2	Q17RS7
GEN1	ENST00000317402.11	TSL:2	c.1971A>G	p.Glu657Glu	synonymous	Exon 14 of 14	ENSP00000318977.7	Q17RS7
GEN1	ENST00000862145.1		c.1971A>G	p.Glu657Glu	synonymous	Exon 14 of 14	ENSP00000532204.1

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71325

AN:

151950

Hom.:

19073

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.617

Gnomad AMR

AF:

0.617

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.919

Gnomad SAS

AF:

0.779

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.496

GnomAD2 exomes

AF:

0.589

AC:

147641

AN:

250642

AF XY:

0.596

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.747

Gnomad ASJ exome

AF:

0.547

Gnomad EAS exome

AF:

0.923

Gnomad FIN exome

AF:

0.491

Gnomad NFE exome

AF:

0.515

Gnomad OTH exome

AF:

0.569

GnomAD4 exome

AF:

0.548

AC:

800356

AN:

1460788

Hom.:

227683

Cov.:

AF XY:

0.554

AC XY:

402608

AN XY:

726754

show subpopulations

African (AFR)

AF:

0.214

AC:

7178

AN:

33464

American (AMR)

AF:

0.730

AC:

32617

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

14191

AN:

26120

East Asian (EAS)

AF:

0.903

AC:

35811

AN:

39670

South Asian (SAS)

AF:

0.764

AC:

65888

AN:

86238

European-Finnish (FIN)

AF:

0.493

AC:

26303

AN:

53340

Middle Eastern (MID)

AF:

0.543

AC:

3133

AN:

5768

European-Non Finnish (NFE)

AF:

0.523

AC:

581381

AN:

1111146

Other (OTH)

AF:

0.561

AC:

33854

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

18809

37619

56428

75238

94047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16856

33712

50568

67424

84280

<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:

0.469

AC:

71365

AN:

152068

Hom.:

19084

Cov.:

AF XY:

0.479

AC XY:

35588

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.230

AC:

9539

AN:

41496

American (AMR)

AF:

0.618

AC:

9438

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1912

AN:

3468

East Asian (EAS)

AF:

0.919

AC:

4754

AN:

5174

South Asian (SAS)

AF:

0.778

AC:

3756

AN:

4826

European-Finnish (FIN)

AF:

0.500

AC:

5285

AN:

10576

Middle Eastern (MID)

AF:

0.534

AC:

157

AN:

294

European-Non Finnish (NFE)

AF:

0.514

AC:

34904

AN:

67930

Other (OTH)

AF:

0.501

AC:

1057

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1739

3478

5216

6955

8694

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.507

Hom.:

43086

Bravo

AF:

0.466

Asia WGS

AF:

0.809

AC:

2810

AN:

3478

EpiCase

AF:

0.525

EpiControl

AF:

0.526

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.3

(source)

DANN

Benign

0.79

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over