13-30462505-C-G

Position:

• chr13-30462505-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002128.7(HMGB1):​c.471+33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,558,380 control chromosomes in the GnomAD database, including 49,698 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3743 hom., cov: 32)
  • Exomes 𝑓: 0.25 (45955 hom.)
• Consequence: HMGB1 NM_002128.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0540

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGB1	NM_002128.7	c.471+33G>C		intron_variant		ENST00000341423.10	NP_002119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423.10	c.471+33G>C		intron_variant		1	NM_002128.7	ENSP00000345347	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30753 AN: 152012 Hom.: 3738 Cov.: 32

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.222 AC: 55835 AN: 251314 Hom.: 6926 AF XY: 0.223 AC XY: 30235 AN XY: 135844

Gnomad AFR exome AF: 0.0726

Gnomad AMR exome AF: 0.170

Gnomad ASJ exome AF: 0.192

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.346

Gnomad NFE exome AF: 0.261

Gnomad OTH exome AF: 0.224

GnomAD4 exome AF: 0.249 AC: 350551 AN: 1406250 Hom.: 45955 Cov.: 23 AF XY: 0.246 AC XY: 172872 AN XY: 702984

Gnomad4 AFR exome AF: 0.0681

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.177

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.238

GnomAD4 genome AF: 0.202 AC: 30758 AN: 152130 Hom.: 3743 Cov.: 32 AF XY: 0.202 AC XY: 15017 AN XY: 74344

Gnomad4 AFR AF: 0.0782

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.184

Alfa AF: 0.231 Hom.: 858

Bravo AF: 0.182

Asia WGS AF: 0.208 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3742305; hg19: chr13-31036642; COSMIC: COSV58104338; COSMIC: COSV58104338;