13-30598457-A-G

Variant names:

• chr13-30598457-A-G
• rs717651
• NM_001313893.1:c.-15+18214T>C

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+18214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,180 control chromosomes in the GnomAD database, including 23,334 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 0.52 (23334 hom., cov: 33)
• Consequence: HMGB1 NM_001313893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.614
• Publications: 4 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGB1	NM_001313893.1	c.-15+18214T>C		intron_variant	Intron 1 of 4		NP_001300822.1
HMGB1	NM_001370340.1	c.-15+18759T>C		intron_variant	Intron 1 of 4		NP_001357269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000405805.5	c.-15+18214T>C		intron_variant	Intron 1 of 4	2		ENSP00000384678.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79537 AN: 152062 Hom.: 23296 Cov.: 33

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.523 AC: 79623 AN: 152180 Hom.: 23334 Cov.: 33 AF XY: 0.514 AC XY: 38254 AN XY: 74392

African (AFR) AF: 0.794 AC: 32977 AN: 41524

American (AMR) AF: 0.452 AC: 6918 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1554 AN: 3472

East Asian (EAS) AF: 0.163 AC: 843 AN: 5182

South Asian (SAS) AF: 0.492 AC: 2372 AN: 4824

European-Finnish (FIN) AF: 0.335 AC: 3541 AN: 10570

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.437 AC: 29726 AN: 68002

Other (OTH) AF: 0.522 AC: 1104 AN: 2116

Alfa AF: 0.469 Hom.: 67834

Bravo AF: 0.542

Asia WGS AF: 0.370 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.0
DANN	Benign	0.54
PhyloP100		0.61
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: rs717651; hg19: chr13-31172594;