rs4353357

Variant names:

• chr13-30474506-G-A
• rs4353357
• NM_001313893.1:c.-14-10812C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-30474506-G-A
• chr13-30474506-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001313893.1(HMGB1):​c.-14-10812C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,154 control chromosomes in the GnomAD database, including 3,733 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 0.22 (3733 hom., cov: 32)
• Consequence: HMGB1 NM_001313893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGB1	NM_001313893.1	c.-14-10812C>T		intron_variant	Intron 1 of 4		NP_001300822.1
HMGB1	NM_001370340.1	c.-14-10812C>T		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.-14-10812C>T		intron_variant	Intron 1 of 4	2		ENSP00000384678.1
ENSG00000285840	ENST00000648233.2	n.300+4896G>A		intron_variant	Intron 2 of 3
ENSG00000285840	ENST00000819189.1	n.553-6739G>A		intron_variant	Intron 1 of 1
ENSG00000285840	ENST00000819190.1	n.504-5924G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33450 AN: 152036 Hom.: 3732 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.220 AC: 33456 AN: 152154 Hom.: 3733 Cov.: 32 AF XY: 0.220 AC XY: 16378 AN XY: 74382

African (AFR) AF: 0.177 AC: 7366 AN: 41514

American (AMR) AF: 0.233 AC: 3562 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3470

East Asian (EAS) AF: 0.281 AC: 1455 AN: 5170

South Asian (SAS) AF: 0.212 AC: 1020 AN: 4822

European-Finnish (FIN) AF: 0.197 AC: 2089 AN: 10580

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16333 AN: 67992

Other (OTH) AF: 0.247 AC: 522 AN: 2112

Alfa AF: 0.229 Hom.: 8471

Bravo AF: 0.220

Asia WGS AF: 0.241 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.67
PhyloP100		-0.45
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: rs4353357; hg19: chr13-31048643;