Genetic Variant GON4L:c.4727-10G>C (chr1-155762384-C-G) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001282860.2(GON4L):c.4727-10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00942 in 1,595,134 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0074 ( 5 hom., cov: 31)

Exomes 𝑓: 0.0096 ( 91 hom. )

Consequence

GON4L
NM_001282860.2 intron

Scores

Splicing: ADA: 0.0001062

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.604

Publications

1 publications found

Variant links:

Genes affected

GON4L (HGNC:25973): (gon-4 like) Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to act upstream of or within B cell differentiation. Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

GON4L Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

GON4L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 1-155762384-C-G is Benign according to our data. Variant chr1-155762384-C-G is described in ClinVar as Benign. ClinVar VariationId is 3057151.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GON4L	NM_001282860.2 link	c.4727-10G>C		intron_variant	Intron 22 of 31	ENST00000368331.6	NP_001269789.1	Q3T8J9-1A4PB67

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GON4L	ENST00000368331.6 link	c.4727-10G>C	intron_variant	Intron 22 of 31	1	NM_001282860.2	ENSP00000357315.1	Q3T8J9-1
GON4L	ENST00000615926.4 link	c.4727-10G>C	intron_variant	Intron 22 of 31	1		ENSP00000483100.1	Q3T8J9-1
GON4L	ENST00000271883.9 link	c.4727-10G>C	intron_variant	Intron 22 of 31	5		ENSP00000271883.5	Q3T8J9-3
GON4L	ENST00000437809.5 link	c.4727-10G>C	intron_variant	Intron 22 of 31	5		ENSP00000396117.1	Q3T8J9-3

Frequencies

GnomAD3 genomes

AF:

0.00745

AC:

1134

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00195

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0103

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00749

AC:

1782

AN:

237944

AF XY:

0.00745

show subpopulations

Gnomad AFR exome

AF:

0.00217

Gnomad AMR exome

AF:

0.00826

Gnomad ASJ exome

AF:

0.000887

Gnomad EAS exome

AF:

0.000112

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.0108

Gnomad OTH exome

AF:

0.0101

GnomAD4 exome

AF:

0.00963

AC:

13896

AN:

1442792

Hom.:

Cov.:

AF XY:

0.00925

AC XY:

6617

AN XY:

714978

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

33250

American (AMR)

AF:

0.00930

AC:

409

AN:

43972

Ashkenazi Jewish (ASJ)

AF:

0.000912

AC:

AN:

25210

East Asian (EAS)

AF:

0.0000509

AC:

AN:

39330

South Asian (SAS)

AF:

0.00129

AC:

108

AN:

83994

European-Finnish (FIN)

AF:

0.00885

AC:

468

AN:

52896

Middle Eastern (MID)

AF:

0.000876

AC:

AN:

5706

European-Non Finnish (NFE)

AF:

0.0113

AC:

12382

AN:

1098828

Other (OTH)

AF:

0.00725

AC:

432

AN:

59606

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

575

1151

1726

2302

2877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.00744

AC:

1134

AN:

152342

Hom.:

Cov.:

AF XY:

0.00767

AC XY:

571

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

41580

American (AMR)

AF:

0.0110

AC:

169

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0131

AC:

139

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0103

AC:

704

AN:

68036

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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:

0.00379

Hom.:

Bravo

AF:

0.00731

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GON4L-related disorder

Benign:1

Aug 06, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.0

(source)

DANN

Benign

0.54

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.038

SpliceAI score (max)

0.11

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