13-30459175-C-CTTAA

Position:

• chr13-30459175-C-CTTAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002128.7(HMGB1):​c.*2181_*2182insTTAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (5979 hom., cov: 19)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 NM_002128.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.255

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 -10 ACMG points.

• BP6: Variant 13-30459175-C-CTTAA is Benign according to our data. Variant chr13-30459175-C-CTTAA is described in ClinVar as [Benign]. Clinvar id is 1289616.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGB1	NM_002128.7	c.*2181_*2182insTTAA		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.*2181_*2182insTTAA		3_prime_UTR_variant	5/5	1	NM_002128.7	ENSP00000345347.5
HMGB1	ENST00000405805	c.*2181_*2182insTTAA		3_prime_UTR_variant	5/5	2		ENSP00000384678.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41817 AN: 151698 Hom.: 5972 Cov.: 19

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.230

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.276 AC: 41846 AN: 151814 Hom.: 5979 Cov.: 19 AF XY: 0.272 AC XY: 20206 AN XY: 74172

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.233

Alfa AF: 0.292 Hom.: 823

Bravo AF: 0.265

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 28, 2020

This variant is associated with the following publications: (PMID: 31777261) -

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: rs10628595; hg19: chr13-31033312;