13-30461330-GAAA-GAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_002128.7(HMGB1):c.*26_*27insTT 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 0.00016 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0038 (0 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd at 24 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_002128.7	c.*26_*27insTT		3_prime_UTR_variant	5/5	ENST00000341423.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGB1	ENST00000341423.10	c.*26_*27insTT		3_prime_UTR_variant	5/5	1	NM_002128.7	P1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 24 AN: 146240 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000134

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.000531

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000895

Gnomad OTH AF: 0.000499

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00376 AC: 4907 AN: 1306418 Hom.: 0 Cov.: 32 AF XY: 0.00370 AC XY: 2382 AN XY: 643580

Gnomad4 AFR exome AF: 0.000571

Gnomad4 AMR exome AF: 0.00264

Gnomad4 ASJ exome AF: 0.00265

Gnomad4 EAS exome AF: 0.00393

Gnomad4 SAS exome AF: 0.00249

Gnomad4 FIN exome AF: 0.00877

Gnomad4 NFE exome AF: 0.00378

Gnomad4 OTH exome AF: 0.00338

GnomAD4 genome AF: 0.000164 AC: 24 AN: 146326 Hom.: 0 Cov.: 17 AF XY: 0.000225 AC XY: 16 AN XY: 71246

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00176

Gnomad4 SAS AF: 0.000212

Gnomad4 FIN AF: 0.000531

Gnomad4 NFE AF: 0.0000895

Gnomad4 OTH AF: 0.000495

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: rs41376448; hg19: chr13-31035467;