13-30467458-C-T

Position:

• chr13-30467458-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000285840 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
HMGB1	NM_001313893.1	c.-14-3764G>A		intron_variant			NP_001300822.1
HMGB1	NM_001370340.1	c.-14-3764G>A		intron_variant			NP_001357269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000405805.5	c.-14-3764G>A		intron_variant		2		ENSP00000384678.1
ENSG00000285840	ENST00000648233.2	n.176+1166C>T		intron_variant

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

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.507

Gnomad4 EAS AF: 0.726

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.501

Alfa AF: 0.480 Hom.: 27076

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

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: rs1412125; hg19: chr13-31041595; COSMIC: COSV58105615; COSMIC: COSV58105615;