rs1331697

Variant names:

• chr13-30558996-C-T
• rs1331697
• NM_001313893.1:c.-15+57675G>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+57675G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 152,060 control chromosomes in the GnomAD database, including 13,137 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 0.40 (13137 hom., cov: 32)
• Consequence: HMGB1 NM_001313893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGB1	NM_001313893.1	c.-15+57675G>A		intron_variant	Intron 1 of 4		NP_001300822.1
HMGB1	NM_001370340.1	c.-15+58220G>A		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+57675G>A		intron_variant	Intron 1 of 4	2		ENSP00000384678.1

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60997 AN: 151942 Hom.: 13112 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.402 AC: 61076 AN: 152060 Hom.: 13137 Cov.: 32 AF XY: 0.407 AC XY: 30282 AN XY: 74318

African (AFR) AF: 0.515 AC: 21362 AN: 41466

American (AMR) AF: 0.381 AC: 5821 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3470

East Asian (EAS) AF: 0.684 AC: 3541 AN: 5174

South Asian (SAS) AF: 0.436 AC: 2102 AN: 4824

European-Finnish (FIN) AF: 0.406 AC: 4280 AN: 10554

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.314 AC: 21323 AN: 67990

Other (OTH) AF: 0.401 AC: 847 AN: 2110

Alfa AF: 0.345 Hom.: 21147

Bravo AF: 0.408

Asia WGS AF: 0.585 AC: 2033 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	0.022
DANN	Benign	0.39
PhyloP100		-2.7
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: rs1331697; hg19: chr13-31133133;