dbSNP rs1060348: HMGB1:p.Phe103Phe (chr13-30462700-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002128.7(HMGB1):c.309C>T(p.Phe103Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.0356 in 1,607,636 control chromosomes in the GnomAD database, including 2,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.082 ( 1160 hom., cov: 32)

Exomes 𝑓: 0.031 ( 1529 hom. )

Consequence

HMGB1
NM_002128.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.61

Publications

13 publications found

Variant links:

Genes affected

HMGB1 (HGNC:4983): (high mobility group box 1) This gene encodes a protein that belongs to the High Mobility Group-box superfamily. The encoded non-histone, nuclear DNA-binding protein regulates transcription, and is involved in organization of DNA. This protein plays a role in several cellular processes, including inflammation, cell differentiation and tumor cell migration. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2015]

HMGB1 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: G2P

HMGB1 links:

ENSG00000285840 (HGNC:):

ENSG00000285840 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 13-30462700-G-A is Benign according to our data. Variant chr13-30462700-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055268.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGB1	NM_002128.7 link	c.309C>T	p.Phe103Phe	synonymous_variant	Exon 4 of 5	ENST00000341423.10	NP_002119.1	P09429A0A024RDR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423.10 link	c.309C>T	p.Phe103Phe	synonymous_variant	Exon 4 of 5	1	NM_002128.7	ENSP00000345347.5		P09429

Frequencies

GnomAD3 genomes

AF:

0.0822

AC:

12499

AN:

151964

Hom.:

1158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0259

Gnomad OTH

AF:

0.0714

GnomAD2 exomes

AF:

0.0350

AC:

8626

AN:

246658

AF XY:

0.0314

show subpopulations

Gnomad AFR exome

AF:

0.235

Gnomad AMR exome

AF:

0.0254

Gnomad ASJ exome

AF:

0.0328

Gnomad EAS exome

AF:

0.000822

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.0248

Gnomad OTH exome

AF:

0.0342

GnomAD4 exome

AF:

0.0307

AC:

44619

AN:

1455554

Hom.:

1529

Cov.:

AF XY:

0.0297

AC XY:

21535

AN XY:

724028

show subpopulations

African (AFR)

AF:

0.239

AC:

7865

AN:

32908

American (AMR)

AF:

0.0267

AC:

1161

AN:

43428

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

827

AN:

25882

East Asian (EAS)

AF:

0.000403

AC:

AN:

39668

South Asian (SAS)

AF:

0.0179

AC:

1513

AN:

84754

European-Finnish (FIN)

AF:

0.0130

AC:

695

AN:

53380

Middle Eastern (MID)

AF:

0.0535

AC:

307

AN:

5734

European-Non Finnish (NFE)

AF:

0.0269

AC:

29852

AN:

1109712

Other (OTH)

AF:

0.0397

AC:

2383

AN:

60088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

1836

3671

5507

7342

9178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1272

2544

3816

5088

6360

<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:

0.0824

AC:

12533

AN:

152082

Hom.:

1160

Cov.:

AF XY:

0.0801

AC XY:

5951

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.233

AC:

9644

AN:

41438

American (AMR)

AF:

0.0385

AC:

589

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

112

AN:

3472

East Asian (EAS)

AF:

0.000964

AC:

AN:

5188

South Asian (SAS)

AF:

0.0195

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0101

AC:

107

AN:

10580

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0259

AC:

1762

AN:

67976

Other (OTH)

AF:

0.0730

AC:

154

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

502

1004

1506

2008

2510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<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:

0.0436

Hom.:

303

Bravo

AF:

0.0917

Asia WGS

AF:

0.0320

AC:

111

AN:

3478

EpiCase

AF:

0.0284

EpiControl

AF:

0.0268

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HMGB1-related disorder

Benign:1

May 29, 2024

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

-0.47

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

5.6

Mutation Taster

=84/16

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

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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