13-30461330-GAAA-GAAAA

Position:

• chr13-30461330-GAAA-GAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002128.7(HMGB1):​c.*26dupT variant causes a 3 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 0.20 (3496 hom., cov: 17)
  • Exomes 𝑓: 0.22 (8133 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 NM_002128.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGB1	NM_002128.7	c.*26dupT		3_prime_UTR_variant	5/5	ENST00000341423.10	NP_002119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423	c.*26dupT		3_prime_UTR_variant	5/5	1	NM_002128.7	ENSP00000345347.5

Frequencies

GnomAD3 genomes AF: 0.202 AC: 29513 AN: 146150 Hom.: 3491 Cov.: 17

Gnomad AFR AF: 0.0780

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.263 AC: 37162 AN: 141356 Hom.: 1835 AF XY: 0.263 AC XY: 20049 AN XY: 76304

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.235

Gnomad ASJ exome AF: 0.259

Gnomad EAS exome AF: 0.257

Gnomad SAS exome AF: 0.209

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.280

Gnomad OTH exome AF: 0.280

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.217 AC: 267177 AN: 1229630 Hom.: 8133 Cov.: 32 AF XY: 0.216 AC XY: 130900 AN XY: 605748

Gnomad4 AFR exome AF: 0.0643

Gnomad4 AMR exome AF: 0.169

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.217

GnomAD4 genome AF: 0.202 AC: 29518 AN: 146236 Hom.: 3496 Cov.: 17 AF XY: 0.202 AC XY: 14360 AN XY: 71182

Gnomad4 AFR AF: 0.0779

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.178

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.360

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.186

Bravo AF: 0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs41376448; hg19: chr13-31035467;