rs1060348

chr13-30462700-G-A

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.309C>T(p.Phe103=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0356 in 1,607,636 control chromosomes in the GnomAD database, including 2,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.082 (1160 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1529 hom.)
• Consequence: HMGB1 NM_002128.7 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.61

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=-0.47).
• BP6: Variant 13-30462700-G-A is Benign according to our data. Variant chr13-30462700-G-A is described in ClinVar as [Benign]. Clinvar id is 3055268.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_002128.7	c.309C>T	p.Phe103=	synonymous_variant	4/5	ENST00000341423.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGB1	ENST00000341423.10	c.309C>T	p.Phe103=	synonymous_variant	4/5	1	NM_002128.7	P1

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12499 AN: 151964 Hom.: 1158 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0714

GnomAD3 exomes AF: 0.0350 AC: 8626 AN: 246658 Hom.: 493 AF XY: 0.0314 AC XY: 4200 AN XY: 133644

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.0254

Gnomad ASJ exome AF: 0.0328

Gnomad EAS exome AF: 0.000822

Gnomad SAS exome AF: 0.0174

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.0248

Gnomad OTH exome AF: 0.0342

GnomAD4 exome AF: 0.0307 AC: 44619 AN: 1455554 Hom.: 1529 Cov.: 32 AF XY: 0.0297 AC XY: 21535 AN XY: 724028

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.0267

Gnomad4 ASJ exome AF: 0.0320

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.0179

Gnomad4 FIN exome AF: 0.0130

Gnomad4 NFE exome AF: 0.0269

Gnomad4 OTH exome AF: 0.0397

GnomAD4 genome AF: 0.0824 AC: 12533 AN: 152082 Hom.: 1160 Cov.: 32 AF XY: 0.0801 AC XY: 5951 AN XY: 74336

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0385

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.0101

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.0730

Alfa AF: 0.0401 Hom.: 175

Bravo AF: 0.0917

Asia WGS AF: 0.0320 AC: 111 AN: 3478

EpiCase AF: 0.0284

EpiControl AF: 0.0268

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HMGB1-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 14, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
Cadd	Benign	13
Dann	Benign	0.85

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: rs1060348; hg19: chr13-31036837;