Genetic Variant HMGB1:c.-469_-465delTTTTT (chr13-30464144-TAAAAA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000399489.5(HMGB1):c.-469_-465delTTTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 779,746 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000095 ( 0 hom. )

Consequence

HMGB1
ENST00000399489.5 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.35

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

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.-14-455_-14-451delTTTTT	intron	N/A	NP_002119.1	P09429
HMGB1	NM_001313892.2		c.-15+12_-15+16delTTTTT	intron	N/A	NP_001300821.1	P09429
HMGB1	NM_001313893.1		c.-14-455_-14-451delTTTTT	intron	N/A	NP_001300822.1	P09429

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGB1	ENST00000399489.5	TSL:1	c.-469_-465delTTTTT	5_prime_UTR	Exon 1 of 5	ENSP00000382412.1	Q5T7C4
HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.-14-455_-14-451delTTTTT	intron	N/A	ENSP00000345347.5	P09429
HMGB1	ENST00000468384.1	TSL:1	n.120-455_120-451delTTTTT	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00000668

AC:

AN:

149590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000952

AC:

AN:

630156

Hom.:

AF XY:

0.0000171

AC XY:

AN XY:

292064

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

12984

American (AMR)

AF:

0.00

AC:

AN:

726

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3850

East Asian (EAS)

AF:

0.00

AC:

AN:

2738

South Asian (SAS)

AF:

0.00

AC:

AN:

12576

European-Finnish (FIN)

AF:

0.00

AC:

AN:

232

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1248

European-Non Finnish (NFE)

AF:

0.0000104

AC:

AN:

575212

Other (OTH)

AF:

0.00

AC:

AN:

20590

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.00000668

AC:

AN:

149590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72906

show subpopulations

African (AFR)

AF:

0.0000245

AC:

AN:

40858

American (AMR)

AF:

0.00

AC:

AN:

15008

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.00

AC:

AN:

4760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9790

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67366

Other (OTH)

AF:

0.00

AC:

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

2131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.3

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over