rs1045411

chr13-30459095-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002128.7(HMGB1):c.*2262G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,060 control chromosomes in the GnomAD database, including 3,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3754 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 NM_002128.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.838

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-30459095-C-T is Benign according to our data. Variant chr13-30459095-C-T is described in ClinVar as [Benign]. Clinvar id is 1250264.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_002128.7	c.*2262G>A		3_prime_UTR_variant	5/5	ENST00000341423.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGB1	ENST00000341423.10	c.*2262G>A		3_prime_UTR_variant	5/5	1	NM_002128.7	P1
HMGB1	ENST00000405805.5	c.*2262G>A		3_prime_UTR_variant	5/5	2		P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30699 AN: 151942 Hom.: 3749 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.178

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: 0.202 AC: 30703 AN: 152060 Hom.: 3754 Cov.: 32 AF XY: 0.202 AC XY: 14977 AN XY: 74302

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.183

Alfa AF: 0.235 Hom.: 4533

Bravo AF: 0.182

Asia WGS AF: 0.209 AC: 729 AN: 3474

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

Jan 10, 2019

This variant is associated with the following publications: (PMID: 28423715) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.075
Dann	Benign	0.53

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: rs1045411; hg19: chr13-31033232;