13-30463766-G-C

Position:

• chr13-30463766-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399489.5(HMGB1):​c.-86C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,003,432 control chromosomes in the GnomAD database, including 30,369 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 0.20 (3676 hom., cov: 33)
  • Exomes 𝑓: 0.24 (26693 hom.)
• Consequence: HMGB1 ENST00000399489.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_002128.7	c.-14-72C>G		intron_variant		ENST00000341423.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGB1	ENST00000341423.10	c.-14-72C>G		intron_variant		1	NM_002128.7	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30412 AN: 152002 Hom.: 3672 Cov.: 33

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.240 AC: 204445 AN: 851312 Hom.: 26693 Cov.: 11 AF XY: 0.236 AC XY: 103046 AN XY: 435800

Gnomad4 AFR exome AF: 0.0664

Gnomad4 AMR exome AF: 0.168

Gnomad4 ASJ exome AF: 0.188

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.200 AC: 30419 AN: 152120 Hom.: 3676 Cov.: 33 AF XY: 0.199 AC XY: 14831 AN XY: 74360

Gnomad4 AFR AF: 0.0773

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.266

Gnomad4 OTH AF: 0.183

Alfa AF: 0.153 Hom.: 374

Bravo AF: 0.180

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.45

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: rs2249825; hg19: chr13-31037903;