rs7983751

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_001313893.1	c.-14-56190A>T		intron_variant
HMGB1	NM_001370340.1	c.-14-56190A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGB1	ENST00000405805.5	c.-14-56190A>T		intron_variant		2		P1

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

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.707

Gnomad4 ASJ AF: 0.654

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.685

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.4
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs7983751; hg19: chr13-31094021;