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GeneBe

13-30461426-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002128.7(HMGB1):c.579T>C(p.Asp193=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,589,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

HMGB1
NM_002128.7 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.171
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 -11 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=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-30461426-A-G is Benign according to our data. Variant chr13-30461426-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2643711.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=-0.171 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HMGB1NM_002128.7 linkuse as main transcriptc.579T>C p.Asp193= synonymous_variant 5/5 ENST00000341423.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HMGB1ENST00000341423.10 linkuse as main transcriptc.579T>C p.Asp193= synonymous_variant 5/51 NM_002128.7 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000213
AC:
32
AN:
150342
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000492
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000265
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000369
Gnomad OTH
AF:
0.000483
GnomAD3 exomes
AF:
0.000267
AC:
41
AN:
153458
Hom.:
0
AF XY:
0.000246
AC XY:
20
AN XY:
81338
show subpopulations
Gnomad AFR exome
AF:
0.000243
Gnomad AMR exome
AF:
0.000334
Gnomad ASJ exome
AF:
0.000235
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000414
Gnomad OTH exome
AF:
0.000923
GnomAD4 exome
AF:
0.000260
AC:
374
AN:
1439484
Hom.:
0
Cov.:
32
AF XY:
0.000285
AC XY:
204
AN XY:
715082
show subpopulations
Gnomad4 AFR exome
AF:
0.000123
Gnomad4 AMR exome
AF:
0.000405
Gnomad4 ASJ exome
AF:
0.000312
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000282
Gnomad4 OTH exome
AF:
0.000439
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000213
AC:
32
AN:
150440
Hom.:
0
Cov.:
31
AF XY:
0.000150
AC XY:
11
AN XY:
73448
show subpopulations
Gnomad4 AFR
AF:
0.0000491
Gnomad4 AMR
AF:
0.000264
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000369
Gnomad4 OTH
AF:
0.000479
Alfa
AF:
0.000192
Hom.:
0

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenSep 01, 2022HMGB1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
4.0
Dann
Benign
0.48
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8

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: rs10444632; hg19: chr13-31035563; API