chr13-30462505-C-G

Variant names:

• chr13-30462505-C-G
• rs3742305
• NM_002128.7:c.471+33G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 publications found

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]

HMGB1 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000285840 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HMGB1	NM_002128.7	c.471+33G>C		intron_variant	Intron 4 of 4	ENST00000341423.10	NP_002119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423.10	c.471+33G>C		intron_variant	Intron 4 of 4	1	NM_002128.7	ENSP00000345347.5

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

GnomAD2 exomes AF: 0.222 AC: 55835 AN: 251314 AF XY: 0.223

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 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

African (AFR) AF: 0.0681 AC: 2204 AN: 32384

American (AMR) AF: 0.168 AC: 7501 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4875 AN: 25766

East Asian (EAS) AF: 0.177 AC: 6977 AN: 39418

South Asian (SAS) AF: 0.151 AC: 12825 AN: 84996

European-Finnish (FIN) AF: 0.348 AC: 18536 AN: 53240

Middle Eastern (MID) AF: 0.154 AC: 872 AN: 5654

European-Non Finnish (NFE) AF: 0.266 AC: 282819 AN: 1061668

Other (OTH) AF: 0.238 AC: 13942 AN: 58472

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

African (AFR) AF: 0.0782 AC: 3249 AN: 41540

American (AMR) AF: 0.170 AC: 2589 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 627 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1098 AN: 5174

South Asian (SAS) AF: 0.139 AC: 671 AN: 4824

European-Finnish (FIN) AF: 0.359 AC: 3787 AN: 10546

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18075 AN: 67996

Other (OTH) AF: 0.184 AC: 390 AN: 2116

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
PhyloP100		-0.054
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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