13-30558575-C-T

Variant names:

• chr13-30558575-C-T
• rs1570613
• NM_001313893.1:c.-15+58096G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001313893.1(HMGB1):​c.-15+58096G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 152,046 control chromosomes in the GnomAD database, including 36,887 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 0.68 (36887 hom., cov: 31)
• Consequence: HMGB1 NM_001313893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 8 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001313893.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	NM_001313893.1		c.-15+58096G>A		intron	N/A	NP_001300822.1	P09429
	HMGB1	NM_001370340.1		c.-15+58641G>A		intron	N/A	NP_001357269.1	P09429

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000405805.5	TSL:2	c.-15+58096G>A		intron	N/A	ENSP00000384678.1	P09429
	HMGB1	ENST00000897840.1		c.-15+58641G>A		intron	N/A	ENSP00000567899.1
	HMGB1	ENST00000897841.1		c.-15+59643G>A		intron	N/A	ENSP00000567900.1

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103599 AN: 151928 Hom.: 36873 Cov.: 31

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.774

Gnomad ASJ AF: 0.736

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.735

Gnomad OTH AF: 0.715

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.682 AC: 103660 AN: 152046 Hom.: 36887 Cov.: 31 AF XY: 0.693 AC XY: 51494 AN XY: 74340

African (AFR) AF: 0.463 AC: 19175 AN: 41396

American (AMR) AF: 0.775 AC: 11850 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.736 AC: 2556 AN: 3472

East Asian (EAS) AF: 0.922 AC: 4774 AN: 5178

South Asian (SAS) AF: 0.848 AC: 4091 AN: 4826

European-Finnish (FIN) AF: 0.832 AC: 8803 AN: 10582

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.735 AC: 49944 AN: 67978

Other (OTH) AF: 0.716 AC: 1514 AN: 2114

Alfa AF: 0.724 Hom.: 76707

Bravo AF: 0.666

Asia WGS AF: 0.858 AC: 2983 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.3
DANN	Benign	0.68
PhyloP100		0.031
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: rs1570613; hg19: chr13-31132712;