13-30464144-TAA-T

Position:

• chr13-30464144-TAA-T

Variant summary

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

The ENST00000399489.5(HMGB1):​c.-466_-465delTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0269 in 709,112 control chromosomes in the GnomAD database, including 99 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.018 (28 hom., cov: 0)
  • Exomes 𝑓: 0.029 (71 hom.)
• Consequence: HMGB1 ENST00000399489.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGB1	NM_002128.7	c.-14-452_-14-451delTT		intron_variant		ENST00000341423.10	NP_002119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423.10	c.-14-452_-14-451delTT		intron_variant		1	NM_002128.7	ENSP00000345347.5

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2615 AN: 149386 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.0308

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.0230

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.0267

Gnomad FIN AF: 0.00298

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0137

Gnomad OTH AF: 0.0162

GnomAD4 exome AF: 0.0293 AC: 16423 AN: 559628 Hom.: 71 AF XY: 0.0298 AC XY: 7729 AN XY: 259690

Gnomad4 AFR exome AF: 0.0466

Gnomad4 AMR exome AF: 0.0173

Gnomad4 ASJ exome AF: 0.0345

Gnomad4 EAS exome AF: 0.00867

Gnomad4 SAS exome AF: 0.0547

Gnomad4 FIN exome AF: 0.00485

Gnomad4 NFE exome AF: 0.0285

Gnomad4 OTH exome AF: 0.0287

GnomAD4 genome AF: 0.0175 AC: 2618 AN: 149484 Hom.: 28 Cov.: 0 AF XY: 0.0167 AC XY: 1220 AN XY: 72902

Gnomad4 AFR AF: 0.0309

Gnomad4 AMR AF: 0.0101

Gnomad4 ASJ AF: 0.0230

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.0263

Gnomad4 FIN AF: 0.00298

Gnomad4 NFE AF: 0.0137

Gnomad4 OTH AF: 0.0160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs5802568; hg19: chr13-31038281;