13-30461330-GAAA-GAA

Variant names:

• chr13-30461330-GA-G
• rs41376448
• NM_002128.7:c.*26delT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002128.7(HMGB1):​c.*26delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.067 (1057 hom., cov: 17)
  • Exomes 𝑓: 0.0049 (339 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 NM_002128.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 6 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002128.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	NM_002128.7	MANE Select	c.*26delT		3_prime_UTR	Exon 5 of 5	NP_002119.1
	HMGB1	NM_001313892.2		c.*26delT		3_prime_UTR	Exon 5 of 5	NP_001300821.1
	HMGB1	NM_001313893.1		c.*26delT		3_prime_UTR	Exon 5 of 5	NP_001300822.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.*26delT		3_prime_UTR	Exon 5 of 5	ENSP00000345347.5
	HMGB1	ENST00000399489.5	TSL:1	c.*247delT		3_prime_UTR	Exon 5 of 5	ENSP00000382412.1
	HMGB1	ENST00000339872.8	TSL:2	c.*26delT		3_prime_UTR	Exon 5 of 5	ENSP00000343040.4

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 9665 AN: 145332 Hom.: 1054 Cov.: 17

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.00700

Gnomad EAS AF: 0.00234

Gnomad SAS AF: 0.00169

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0427

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00488 AC: 6436 AN: 1318820 Hom.: 339 Cov.: 32 AF XY: 0.00430 AC XY: 2794 AN XY: 649738

African (AFR) AF: 0.173 AC: 4412 AN: 25484

American (AMR) AF: 0.0128 AC: 372 AN: 28970

Ashkenazi Jewish (ASJ) AF: 0.00441 AC: 87 AN: 19750

East Asian (EAS) AF: 0.00611 AC: 220 AN: 36014

South Asian (SAS) AF: 0.000866 AC: 58 AN: 66938

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46698

Middle Eastern (MID) AF: 0.0111 AC: 39 AN: 3524

European-Non Finnish (NFE) AF: 0.000528 AC: 548 AN: 1037796

Other (OTH) AF: 0.0130 AC: 700 AN: 53646

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0666 AC: 9687 AN: 145418 Hom.: 1057 Cov.: 17 AF XY: 0.0637 AC XY: 4511 AN XY: 70802

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.241 AC: 9071 AN: 37684

American (AMR) AF: 0.0273 AC: 406 AN: 14866

Ashkenazi Jewish (ASJ) AF: 0.00700 AC: 24 AN: 3430

East Asian (EAS) AF: 0.00235 AC: 12 AN: 5108

South Asian (SAS) AF: 0.00149 AC: 7 AN: 4710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9416

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.00112 AC: 75 AN: 67004

Other (OTH) AF: 0.0424 AC: 85 AN: 2006

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.075
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: rs41376448; hg19: chr13-31035467;