13-30461402-TTCCTCC-TTCCTCCTCC

Variant names:

• chr13-30461402-T-TTCC
• rs745673887
• NM_002128.7:c.600_602dupGGA

Variant summary

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

The NM_002128.7(HMGB1):​c.600_602dupGGA​(p.Glu201dup) variant causes a disruptive inframe insertion change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000077 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 NM_002128.7 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.44
• Publications: 0 publications found

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

ENSG00000285840 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	NM_002128.7	MANE Select	c.600_602dupGGA	p.Glu201dup	disruptive_inframe_insertion	Exon 5 of 5	NP_002119.1	P09429
	HMGB1	NM_001313892.2		c.600_602dupGGA	p.Glu201dup	disruptive_inframe_insertion	Exon 5 of 5	NP_001300821.1	P09429
	HMGB1	NM_001313893.1		c.600_602dupGGA	p.Glu201dup	disruptive_inframe_insertion	Exon 5 of 5	NP_001300822.1	P09429

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.600_602dupGGA	p.Glu201dup	disruptive_inframe_insertion	Exon 5 of 5	ENSP00000345347.5	P09429
	HMGB1	ENST00000399489.5	TSL:1	c.*173_*175dupGGA		3_prime_UTR	Exon 5 of 5	ENSP00000382412.1	Q5T7C4
	HMGB1	ENST00000927783.1		c.609_611dupGGA	p.Glu204dup	disruptive_inframe_insertion	Exon 5 of 5	ENSP00000597842.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000152 AC: 2 AN: 131744 AF XY: 0.0000143

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: 0.0000365

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000771 AC: 11 AN: 1426732 Hom.: 1 Cov.: 32 AF XY: 0.00000988 AC XY: 7 AN XY: 708330

African (AFR) AF: 0.00 AC: 0 AN: 31370

American (AMR) AF: 0.00 AC: 0 AN: 36108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24290

East Asian (EAS) AF: 0.00 AC: 0 AN: 39504

South Asian (SAS) AF: 0.00 AC: 0 AN: 80574

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51960

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4062

European-Non Finnish (NFE) AF: 0.00000818 AC: 9 AN: 1100176

Other (OTH) AF: 0.0000341 AC: 2 AN: 58688

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.4

Splicing

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

Other links and lift over

dbSNP: rs745673887; hg19: chr13-31035539;