rs7983751

Variant names:

• chr13-30519884-T-A
• rs7983751
• NM_001313893.1:c.-14-56190A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-30519884-T-A
• chr13-30519884-T-G

Variant summary

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

The NM_001313893.1(HMGB1):​c.-14-56190A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 152,046 control chromosomes in the GnomAD database, including 35,457 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 (35457 hom., cov: 32)
• Consequence: HMGB1 NM_001313893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	NM_001313893.1		c.-14-56190A>T		intron	N/A	NP_001300822.1
	HMGB1	NM_001370340.1		c.-14-56190A>T		intron	N/A	NP_001357269.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000405805.5	TSL:2	c.-14-56190A>T		intron	N/A	ENSP00000384678.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103214 AN: 151928 Hom.: 35431 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.680

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

GnomAD4 genome AF: 0.679 AC: 103266 AN: 152046 Hom.: 35457 Cov.: 32 AF XY: 0.676 AC XY: 50240 AN XY: 74300

African (AFR) AF: 0.591 AC: 24511 AN: 41456

American (AMR) AF: 0.707 AC: 10798 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2271 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2745 AN: 5166

South Asian (SAS) AF: 0.542 AC: 2613 AN: 4822

European-Finnish (FIN) AF: 0.736 AC: 7781 AN: 10568

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50249 AN: 67972

Other (OTH) AF: 0.685 AC: 1447 AN: 2112

Alfa AF: 0.585 Hom.: 1348

Bravo AF: 0.675

Asia WGS AF: 0.572 AC: 1990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.4
DANN	Benign	0.86
PhyloP100		-0.45
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: rs7983751; hg19: chr13-31094021;