13-30467458-C-T

Variant names:

• chr13-30467458-C-T
• rs1412125
• NM_001313893.1:c.-14-3764G>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.-14-3764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,008 control chromosomes in the GnomAD database, including 17,501 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 0.48 (17501 hom., cov: 33)
• Consequence: HMGB1 NM_001313893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210
• Publications: 45 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

ENSG00000285840 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGB1	NM_001313893.1	c.-14-3764G>A		intron_variant	Intron 1 of 4		NP_001300822.1
HMGB1	NM_001370340.1	c.-14-3764G>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.-14-3764G>A		intron_variant	Intron 1 of 4	2		ENSP00000384678.1
ENSG00000285840	ENST00000648233.2	n.176+1166C>T		intron_variant	Intron 1 of 3
ENSG00000285840	ENST00000819189.1	n.553-13787C>T		intron_variant	Intron 1 of 1
ENSG00000285840	ENST00000819190.1	n.504-12972C>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72390 AN: 151890 Hom.: 17504 Cov.: 33

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.507

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.476 AC: 72396 AN: 152008 Hom.: 17501 Cov.: 33 AF XY: 0.481 AC XY: 35754 AN XY: 74294

African (AFR) AF: 0.421 AC: 17462 AN: 41460

American (AMR) AF: 0.462 AC: 7060 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 1759 AN: 3472

East Asian (EAS) AF: 0.726 AC: 3765 AN: 5184

South Asian (SAS) AF: 0.585 AC: 2820 AN: 4822

European-Finnish (FIN) AF: 0.496 AC: 5235 AN: 10544

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32722 AN: 67948

Other (OTH) AF: 0.501 AC: 1057 AN: 2108

Alfa AF: 0.480 Hom.: 66691

Bravo AF: 0.469

Asia WGS AF: 0.603 AC: 2083 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.53
PhyloP100		-0.21
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: rs1412125; hg19: chr13-31041595; COSMIC: COSV58105615; COSMIC: COSV58105615;