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13-30463308-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_002128.7(HMGB1):c.195A>G(p.Lys65=) 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 (★).

Frequency

Genomes: 𝑓 0.074 ( 1346 hom., cov: 33)
Exomes 𝑓: 0.0077 ( 1174 hom. )

Consequence

HMGB1
NM_002128.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter 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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.62).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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 criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.604 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
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 UniProt
HMGB1NM_002128.7 linkuse as main transcriptc.195A>G p.Lys65= synonymous_variant 3/5 ENST00000341423.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HMGB1ENST00000341423.10 linkuse as main transcriptc.195A>G p.Lys65= synonymous_variant 3/51 NM_002128.7 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0734
AC:
11172
AN:
152194
Hom.:
1344
Cov.:
33
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.:
30
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0735
AC:
11198
AN:
152312
Hom.:
1346
Cov.:
33
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:
63
AN:
3478
EpiCase
AF:
0.00164
EpiControl
AF:
0.00130

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

HMGB1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 28, 2019This 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
13
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.

Other links and lift over

dbSNP: rs983723; hg19: chr13-31037445; COSMIC: COSV58105654; COSMIC: COSV58105654; API