Genetic Variant :null (chr1-161363768-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The variant allele was found at a frequency of 0.112 in 232,898 control chromosomes in the GnomAD database, including 2,186 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1420 hom., cov: 32)

Exomes 𝑓: 0.10 ( 766 hom. )

Consequence

Unknown

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0340

Publications

12 publications found

Variant links:

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ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 1-161363768-A-G is Benign according to our data. Variant chr1-161363768-A-G is described in ClinVar as Benign. ClinVar VariationId is 293347.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17801

AN:

152064

Hom.:

1417

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0687

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.104

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0643

Gnomad OTH

AF:

0.0930

GnomAD4 exome

AF:

0.101

AC:

8183

AN:

80718

Hom.:

766

Cov.:

AF XY:

0.0976

AC XY:

3622

AN XY:

37124

show subpopulations

African (AFR)

AF:

0.223

AC:

869

AN:

3890

American (AMR)

AF:

0.0635

AC:

158

AN:

2490

Ashkenazi Jewish (ASJ)

AF:

0.0310

AC:

158

AN:

5100

East Asian (EAS)

AF:

0.303

AC:

3488

AN:

11504

South Asian (SAS)

AF:

0.209

AC:

146

AN:

698

European-Finnish (FIN)

AF:

0.0517

AC:

AN:

Middle Eastern (MID)

AF:

0.0391

AC:

AN:

486

European-Non Finnish (NFE)

AF:

0.0568

AC:

2825

AN:

49754

Other (OTH)

AF:

0.0767

AC:

517

AN:

6738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

392

784

1175

1567

1959

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.117

AC:

17823

AN:

152180

Hom.:

1420

Cov.:

AF XY:

0.120

AC XY:

8914

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.216

AC:

8979

AN:

41512

American (AMR)

AF:

0.0685

AC:

1048

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0282

AC:

AN:

3472

East Asian (EAS)

AF:

0.210

AC:

1084

AN:

5168

South Asian (SAS)

AF:

0.186

AC:

895

AN:

4820

European-Finnish (FIN)

AF:

0.104

AC:

1106

AN:

10596

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0643

AC:

4370

AN:

68002

Other (OTH)

AF:

0.0920

AC:

194

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

768

1535

2303

3070

3838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

198

396

594

792

990

<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:

0.0716

Hom.:

703

Bravo

AF:

0.115

Asia WGS

AF:

0.202

AC:

698

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary pheochromocytoma-paraganglioma

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.28

(source)

DANN

Benign

0.41

PhyloP100

-0.034

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

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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