chr13-30464144-T-TA

Variant names:

• chr13-30464144-T-TA
• rs5802568
• ENST00000399489.5:c.-465dupT

Variant summary

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

The ENST00000399489.5(HMGB1):​c.-465dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000021 (0 hom.)
• 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.-14-451dupT		intron	N/A	NP_002119.1	P09429
	HMGB1	NM_001313892.2		c.-15+16dupT		intron	N/A	NP_001300821.1	P09429
	HMGB1	NM_001313893.1		c.-14-451dupT		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.-465dupT		5_prime_UTR	Exon 1 of 5	ENSP00000382412.1	Q5T7C4
	HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.-14-451dupT		intron	N/A	ENSP00000345347.5	P09429
	HMGB1	ENST00000468384.1	TSL:1	n.120-451dupT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000206 AC: 13 AN: 629714 Hom.: 0 Cov.: 0 AF XY: 0.0000137 AC XY: 4 AN XY: 291876

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

African (AFR) AF: 0.000386 AC: 5 AN: 12954

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3846

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 12564

European-Finnish (FIN) AF: 0.00431 AC: 1 AN: 232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1246

European-Non Finnish (NFE) AF: 0.0000122 AC: 7 AN: 574838

Other (OTH) AF: 0.00 AC: 0 AN: 20570

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 2131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs5802568; hg19: chr13-31038281;