Variant 13-30463308-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_002128.7(HMGB1):c.195A>G(p.Lys65Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,609,224 control chromosomes in the GnomAD database, including 2,520 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.074 ( 1346 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 1174 hom. )

Consequence

HMGB1
NM_002128.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.604

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:

HMGB1 (HGNC:):

HMGB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 13-30463308-T-C is Benign according to our data. Variant chr13-30463308-T-C is described in ClinVar as [Benign]. Clinvar id is 3056340.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.604 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 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.195A>G	p.Lys65Lys	synonymous_variant	3/5	ENST00000341423.10	NP_002119.1	P09429A0A024RDR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423.10 linkuse as main transcript	c.195A>G	p.Lys65Lys	synonymous_variant	3/5	1	NM_002128.7	ENSP00000345347.5		P09429

Frequencies

GnomAD3 genomes

AF:

0.0734

AC:

11172

AN:

152194

Hom.:

1344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00106

Gnomad OTH

AF:

0.0501

GnomAD3 exomes

AF:

0.0193

AC:

4785

AN:

248390

Hom.:

515

AF XY:

0.0146

AC XY:

1958

AN XY:

134464

show subpopulations

Gnomad AFR exome

AF:

0.254

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.00659

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000733

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000947

Gnomad OTH exome

AF:

0.00956

GnomAD4 exome

AF:

0.00768

AC:

11193

AN:

1456912

Hom.:

1174

Cov.:

AF XY:

0.00662

AC XY:

4799

AN XY:

724756

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.0155

Gnomad4 ASJ exome

AF:

0.00621

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000798

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000555

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0735

AC:

11198

AN:

152312

Hom.:

1346

Cov.:

AF XY:

0.0709

AC XY:

5282

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.0284

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00106

Gnomad4 OTH

AF:

0.0496

Alfa

AF:

0.0336

Hom.:

234

Bravo

AF:

0.0832

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00130

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 14, 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

-0.62

CADD

Benign

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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