13-30461402-TTCC-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_002128.7(HMGB1):c.600_602del(p.Glu201del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000421 in 151,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00042 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00040 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 NM_002128.7 inframe_deletion
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.02

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 13-30461402-TTCC-T is Benign according to our data. Variant chr13-30461402-TTCC-T is described in ClinVar as [Benign]. Clinvar id is 2643710.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 64 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_002128.7	c.600_602del	p.Glu201del	inframe_deletion	5/5	ENST00000341423.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HMGB1	ENST00000341423.10	c.600_602del	p.Glu201del	inframe_deletion	5/5	1	NM_002128.7	P1

Frequencies

GnomAD3 genomes AF: 0.000422 AC: 64 AN: 151764 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000704

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000379

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000493 AC: 65 AN: 131744 Hom.: 0 AF XY: 0.000600 AC XY: 42 AN XY: 70052

Gnomad AFR exome AF: 0.000128

Gnomad AMR exome AF: 0.000935

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000378

Gnomad SAS exome AF: 0.00193

Gnomad FIN exome AF: 0.000211

Gnomad NFE exome AF: 0.000128

Gnomad OTH exome AF: 0.000278

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000398 AC: 568 AN: 1426462 Hom.: 0 AF XY: 0.000412 AC XY: 292 AN XY: 708148

Gnomad4 AFR exome AF: 0.000415

Gnomad4 AMR exome AF: 0.000859

Gnomad4 ASJ exome AF: 0.0000412

Gnomad4 EAS exome AF: 0.00162

Gnomad4 SAS exome AF: 0.00171

Gnomad4 FIN exome AF: 0.000154

Gnomad4 NFE exome AF: 0.000262

Gnomad4 OTH exome AF: 0.000392

GnomAD4 genome AF: 0.000421 AC: 64 AN: 151882 Hom.: 0 Cov.: 31 AF XY: 0.000391 AC XY: 29 AN XY: 74244

Gnomad4 AFR AF: 0.000702

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000379

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000325

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

HMGB1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs745673887; hg19: chr13-31035539;