Genetic Variant HMGB1:c.-465delT (chr13-30464144-TA-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000399489.5(HMGB1):c.-465delT variant causes a 5 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 0.95 ( 67581 hom., cov: 0)

Exomes 𝑓: 0.78 ( 175298 hom. )

Consequence

HMGB1
ENST00000399489.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.403

Publications

3 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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000399489.5. 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.-14-451delT	intron	N/A	NP_002119.1	P09429
HMGB1	NM_001313892.2		c.-15+16delT	intron	N/A	NP_001300821.1	P09429
HMGB1	NM_001313893.1		c.-14-451delT	intron	N/A	NP_001300822.1	P09429

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGB1	ENST00000399489.5	TSL:1	c.-465delT	5_prime_UTR	Exon 1 of 5	ENSP00000382412.1	Q5T7C4
HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.-14-451delT	intron	N/A	ENSP00000345347.5	P09429
HMGB1	ENST00000468384.1	TSL:1	n.120-451delT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.949

AC:

141992

AN:

149568

Hom.:

67561

Cov.:

show subpopulations

Gnomad AFR

AF:

0.877

Gnomad AMI

AF:

0.989

Gnomad AMR

AF:

0.969

Gnomad ASJ

AF:

0.967

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.971

Gnomad FIN

AF:

0.986

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.976

Gnomad OTH

AF:

0.963

GnomAD4 exome

AF:

0.778

AC:

490046

AN:

630022

Hom.:

175298

Cov.:

AF XY:

0.779

AC XY:

227370

AN XY:

292006

show subpopulations

African (AFR)

AF:

0.740

AC:

9567

AN:

12926

American (AMR)

AF:

0.787

AC:

571

AN:

726

Ashkenazi Jewish (ASJ)

AF:

0.784

AC:

3017

AN:

3850

East Asian (EAS)

AF:

0.792

AC:

2168

AN:

2738

South Asian (SAS)

AF:

0.770

AC:

9684

AN:

12574

European-Finnish (FIN)

AF:

0.802

AC:

186

AN:

232

Middle Eastern (MID)

AF:

0.768

AC:

958

AN:

1248

European-Non Finnish (NFE)

AF:

0.779

AC:

447887

AN:

575140

Other (OTH)

AF:

0.778

AC:

16008

AN:

20588

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.728

Heterozygous variant carriers

9572

19145

28717

38290

47862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15266

30532

45798

61064

76330

<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:

0.949

AC:

142057

AN:

149666

Hom.:

67581

Cov.:

AF XY:

0.950

AC XY:

69375

AN XY:

72994

show subpopulations

African (AFR)

AF:

0.877

AC:

35901

AN:

40956

American (AMR)

AF:

0.969

AC:

14555

AN:

15022

Ashkenazi Jewish (ASJ)

AF:

0.967

AC:

3325

AN:

3440

East Asian (EAS)

AF:

0.999

AC:

5077

AN:

5084

South Asian (SAS)

AF:

0.971

AC:

4612

AN:

4750

European-Finnish (FIN)

AF:

0.986

AC:

9653

AN:

9790

Middle Eastern (MID)

AF:

0.986

AC:

288

AN:

292

European-Non Finnish (NFE)

AF:

0.976

AC:

65754

AN:

67354

Other (OTH)

AF:

0.963

AC:

1992

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

318

635

953

1270

1588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.970

Hom.:

2131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.40

Mutation Taster

=296/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over