13-30464004-T-TAA

Position:

• chr13-30464004-T-TAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000399489.5(HMGB1):​c.-325_-324insTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00322 in 664,568 control chromosomes in the GnomAD database, including 13 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0033 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (10 hom.)
• Consequence: HMGB1 ENST00000399489.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.740

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.

• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0032 (1638/512336) while in subpopulation MID AF= 0.0249 (27/1084). AF 95% confidence interval is 0.0176. There are 10 homozygotes in gnomad4_exome. There are 783 alleles in male gnomad4_exome subpopulation. Median coverage is 8. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 499 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_002128.7	c.-14-311_-14-310insTT		intron_variant		ENST00000341423.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGB1	ENST00000341423.10	c.-14-311_-14-310insTT		intron_variant		1	NM_002128.7	P1

Frequencies

GnomAD3 genomes AF: 0.00328 AC: 499 AN: 152114 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00385

Gnomad OTH AF: 0.00288

GnomAD4 exome AF: 0.00320 AC: 1638 AN: 512336 Hom.: 10 Cov.: 8 AF XY: 0.00322 AC XY: 783 AN XY: 242802

Gnomad4 AFR exome AF: 0.000106

Gnomad4 AMR exome AF: 0.00531

Gnomad4 ASJ exome AF: 0.00307

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0142

Gnomad4 FIN exome AF: 0.00112

Gnomad4 NFE exome AF: 0.00294

Gnomad4 OTH exome AF: 0.00378

GnomAD4 genome AF: 0.00328 AC: 499 AN: 152232 Hom.: 3 Cov.: 32 AF XY: 0.00372 AC XY: 277 AN XY: 74436

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.00614

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00385

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.00324

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs41497949; hg19: chr13-31038141;