rs41376448

Variant names:

• chr13-30461330-GAAA-G
• rs41376448
• NM_002128.7:c.*24_*26delTTT

Your query was ambiguous. Multiple possible variants found:

• chr13-30461330-GAAA-G
• chr13-30461330-GAAA-GA
• chr13-30461330-GAAA-GAA
• chr13-30461330-GAAA-GAAAA
• chr13-30461330-GAAA-GAAAAA

Variant summary

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

The NM_002128.7(HMGB1):​c.*24_*26delTTT 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: not found (cov: 17)
  • Exomes 𝑓: 0.0000061 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 NM_002128.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.46
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	NM_002128.7	MANE Select	c.*24_*26delTTT		3_prime_UTR	Exon 5 of 5	NP_002119.1	P09429
	HMGB1	NM_001313892.2		c.*24_*26delTTT		3_prime_UTR	Exon 5 of 5	NP_001300821.1	P09429
	HMGB1	NM_001313893.1		c.*24_*26delTTT		3_prime_UTR	Exon 5 of 5	NP_001300822.1	P09429

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.*24_*26delTTT		3_prime_UTR	Exon 5 of 5	ENSP00000345347.5	P09429
	HMGB1	ENST00000399489.5	TSL:1	c.*245_*247delTTT		3_prime_UTR	Exon 5 of 5	ENSP00000382412.1	Q5T7C4
	HMGB1	ENST00000927783.1		c.*24_*26delTTT		3_prime_UTR	Exon 5 of 5	ENSP00000597842.1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000605 AC: 8 AN: 1322170 Hom.: 0 AF XY: 0.00000921 AC XY: 6 AN XY: 651230

African (AFR) AF: 0.00 AC: 0 AN: 28070

American (AMR) AF: 0.00 AC: 0 AN: 28996

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19772

East Asian (EAS) AF: 0.00 AC: 0 AN: 36032

South Asian (SAS) AF: 0.00 AC: 0 AN: 66954

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3544

European-Non Finnish (NFE) AF: 0.00000674 AC: 7 AN: 1038190

Other (OTH) AF: 0.0000185 AC: 1 AN: 53912

GnomAD4 genome Cov.: 17

Alfa AF: 0.00 Hom.: 277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.5

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs41376448;

hg19: chr13-31035467;