Genetic Variant NM_002128.7:c.597_602delGGAGGA (chr13-30461402-TTCCTCC-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002128.7(HMGB1):c.597_602delGGAGGA(p.Glu200_Glu201del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 151,766 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 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HMGB1
NM_002128.7 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.33

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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	HGVSp	Effect	Exon Rank	Protein	UniProt
HMGB1	NM_002128.7	MANE Select	c.597_602delGGAGGA	p.Glu200_Glu201del	disruptive_inframe_deletion	Exon 5 of 5	NP_002119.1	P09429
HMGB1	NM_001313892.2		c.597_602delGGAGGA	p.Glu200_Glu201del	disruptive_inframe_deletion	Exon 5 of 5	NP_001300821.1	P09429
HMGB1	NM_001313893.1		c.597_602delGGAGGA	p.Glu200_Glu201del	disruptive_inframe_deletion	Exon 5 of 5	NP_001300822.1	P09429

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.597_602delGGAGGA	p.Glu200_Glu201del	disruptive_inframe_deletion	Exon 5 of 5	ENSP00000345347.5	P09429
HMGB1	ENST00000399489.5	TSL:1	c.170_175delGGAGGA		3_prime_UTR	Exon 5 of 5	ENSP00000382412.1	Q5T7C4
HMGB1	ENST00000927783.1		c.606_611delGGAGGA	p.Glu203_Glu204del	disruptive_inframe_deletion	Exon 5 of 5	ENSP00000597842.1

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000380

AC:

AN:

131744

AF XY:

0.0000571

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:

0.000141

Gnomad NFE exome

AF:

0.0000365

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000224

AC:

AN:

1426732

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

708330

show subpopulations

African (AFR)

AF:

0.0000319

AC:

AN:

31370

American (AMR)

AF:

0.00

AC:

AN:

36110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24290

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39504

South Asian (SAS)

AF:

0.0000248

AC:

AN:

80574

European-Finnish (FIN)

AF:

0.0000770

AC:

AN:

51960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4062

European-Non Finnish (NFE)

AF:

0.0000200

AC:

AN:

1100174

Other (OTH)

AF:

0.0000170

AC:

AN:

58688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.0000198

AC:

AN:

151766

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74118

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41176

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10564

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000728

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

7.3

Mutation Taster

=137/63

polymorphism

(source)

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