Variant rs1060348 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002128.7(HMGB1):c.309C>T(p.Phe103=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
HMGB1	NM_002128.7 linkuse as main transcript	c.309C>T	p.Phe103=	synonymous_variant	4/5	ENST00000341423.10	NP_002119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423.10 linkuse as main transcript	c.309C>T	p.Phe103=	synonymous_variant	4/5	1	NM_002128.7	ENSP00000345347	P1

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

GnomAD3 exomes

AF:

0.0350

AC:

8626

AN:

246658

Hom.:

493

AF XY:

0.0314

AC XY:

4200

AN XY:

133644

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 SAS exome

AF:

0.0174

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

Gnomad4 AFR exome

AF:

0.239

Gnomad4 AMR exome

AF:

0.0267

Gnomad4 ASJ exome

AF:

0.0320

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.0179

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.0269

Gnomad4 OTH exome

AF:

0.0397

GnomAD4 genome

AF:

0.0824

AC:

12533

AN:

152082

Hom.:

1160

Cov.:

AF XY:

0.0801

AC XY:

5951

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.233

Gnomad4 AMR

AF:

0.0385

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.0259

Gnomad4 OTH

AF:

0.0730

Alfa

AF:

0.0401

Hom.:

175

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 29, 2024

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

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over