Genetic Variant HMGB1:c.*25_*26delTT (chr13-30461330-GAA-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002128.7(HMGB1):c.*25_*26delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HMGB1
NM_002128.7 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.20

Publications

6 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002128.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGB1	NM_002128.7	MANE Select	c.25_26delTT	3_prime_UTR	Exon 5 of 5	NP_002119.1	P09429
HMGB1	NM_001313892.2		c.25_26delTT	3_prime_UTR	Exon 5 of 5	NP_001300821.1	P09429
HMGB1	NM_001313893.1		c.25_26delTT	3_prime_UTR	Exon 5 of 5	NP_001300822.1	P09429

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.25_26delTT	3_prime_UTR	Exon 5 of 5	ENSP00000345347.5	P09429
HMGB1	ENST00000399489.5	TSL:1	c.246_247delTT	3_prime_UTR	Exon 5 of 5	ENSP00000382412.1	Q5T7C4
HMGB1	ENST00000927783.1		c.25_26delTT	3_prime_UTR	Exon 5 of 5	ENSP00000597842.1

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000707

AC:

AN:

141356

AF XY:

0.0000131

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000139

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000113

AC:

AN:

1322166

Hom.:

AF XY:

0.0000123

AC XY:

AN XY:

651226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28070

American (AMR)

AF:

0.00

AC:

AN:

28996

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19772

East Asian (EAS)

AF:

0.00

AC:

AN:

36030

South Asian (SAS)

AF:

0.00

AC:

AN:

66954

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46700

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3544

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1038188

Other (OTH)

AF:

0.0000185

AC:

AN:

53912

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000137

AC:

AN:

146256

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

71156

show subpopulations

African (AFR)

AF:

0.0000260

AC:

AN:

38412

American (AMR)

AF:

0.00

AC:

AN:

14886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3434

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000149

AC:

AN:

67034

Other (OTH)

AF:

0.00

AC:

AN:

2006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over