13-30464144-TAAAAA-TAAAAAAAA

Variant names:

• chr13-30464144-T-TAAA
• rs5802568
• ENST00000399489.5:c.-467_-465dupTTT

Variant summary

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

The ENST00000399489.5(HMGB1):​c.-467_-465dupTTT 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 0.0000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 ENST00000399489.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 3 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 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	NM_002128.7	MANE Select	c.-14-453_-14-451dupTTT		intron	N/A	NP_002119.1	P09429
	HMGB1	NM_001313892.2		c.-15+14_-15+16dupTTT		intron	N/A	NP_001300821.1	P09429
	HMGB1	NM_001313893.1		c.-14-453_-14-451dupTTT		intron	N/A	NP_001300822.1	P09429

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000399489.5	TSL:1	c.-467_-465dupTTT		5_prime_UTR	Exon 1 of 5	ENSP00000382412.1	Q5T7C4
	HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.-14-453_-14-451dupTTT		intron	N/A	ENSP00000345347.5	P09429
	HMGB1	ENST00000468384.1	TSL:1	n.120-453_120-451dupTTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149590 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 630154 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 292064

African (AFR) AF: 0.00 AC: 0 AN: 12984

American (AMR) AF: 0.00 AC: 0 AN: 726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3850

East Asian (EAS) AF: 0.00 AC: 0 AN: 2738

South Asian (SAS) AF: 0.00 AC: 0 AN: 12576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1248

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 575210

Other (OTH) AF: 0.00 AC: 0 AN: 20590

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149590 Hom.: 0 Cov.: 0 AF XY: 0.0000137 AC XY: 1 AN XY: 72906

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 40858

American (AMR) AF: 0.00 AC: 0 AN: 15008

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5096

South Asian (SAS) AF: 0.00 AC: 0 AN: 4760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67366

Other (OTH) AF: 0.00 AC: 0 AN: 2046

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.40

Splicing

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.

Other links and lift over

dbSNP: rs5802568; hg19: chr13-31038281;