13-30463766-G-T

Variant names:

• chr13-30463766-G-T
• rs2249825
• ENST00000399489.5:c.-86C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000399489.5(HMGB1):​c.-86C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,004,980 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: HMGB1 ENST00000399489.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 72 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGB1	NM_002128.7	c.-14-72C>A		intron_variant	Intron 1 of 4	ENST00000341423.10	NP_002119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423.10	c.-14-72C>A		intron_variant	Intron 1 of 4	1	NM_002128.7	ENSP00000345347.5

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000129 AC: 11 AN: 852942 Hom.: 0 Cov.: 11 AF XY: 0.0000115 AC XY: 5 AN XY: 436604

African (AFR) AF: 0.00 AC: 0 AN: 19172

American (AMR) AF: 0.0000782 AC: 2 AN: 25582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16836

East Asian (EAS) AF: 0.00 AC: 0 AN: 32492

South Asian (SAS) AF: 0.00 AC: 0 AN: 52972

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30822

Middle Eastern (MID) AF: 0.000323 AC: 1 AN: 3100

European-Non Finnish (NFE) AF: 0.0000126 AC: 8 AN: 633048

Other (OTH) AF: 0.00 AC: 0 AN: 38918

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74252

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10540

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 374

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.51
PhyloP100		-0.049
PromoterAI		-0.0028	Neutral

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: rs2249825; hg19: chr13-31037903;