Genetic Variant HMGB1:c.-14-3526delA (chr13-30467219-CT-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001313893.1(HMGB1):c.-14-3526delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 152,146 control chromosomes in the GnomAD database, including 126 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.032 ( 126 hom., cov: 32)

Consequence

HMGB1
NM_001313893.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.145

Publications

4 publications found

Variant links:

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

HMGB1 links:

ENSG00000285840 (HGNC:):

ENSG00000285840 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0324 (4927/152146) while in subpopulation NFE AF = 0.0486 (3301/67988). AF 95% confidence interval is 0.0472. There are 126 homozygotes in GnomAd4. There are 2278 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4927 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001313893.1. 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_001313893.1		c.-14-3526delA		intron	N/A	NP_001300822.1	P09429
	HMGB1	NM_001370340.1		c.-14-3526delA		intron	N/A	NP_001357269.1	P09429

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HMGB1	ENST00000405805.5	TSL:2	c.-14-3526delA	intron	N/A	ENSP00000384678.1	P09429
HMGB1	ENST00000897840.1		c.-14-3526delA	intron	N/A	ENSP00000567899.1
HMGB1	ENST00000897841.1		c.-14-3526delA	intron	N/A	ENSP00000567900.1

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4931

AN:

152028

Hom.:

126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00831

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0355

Gnomad ASJ

AF:

0.0952

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0179

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0485

Gnomad OTH

AF:

0.0422

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

GnomAD4 genome

AF:

0.0324

AC:

4927

AN:

152146

Hom.:

126

Cov.:

AF XY:

0.0306

AC XY:

2278

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00826

AC:

343

AN:

41502

American (AMR)

AF:

0.0354

AC:

541

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0952

AC:

330

AN:

3466

East Asian (EAS)

AF:

0.000386

AC:

AN:

5184

South Asian (SAS)

AF:

0.0116

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0179

AC:

190

AN:

10598

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0486

AC:

3301

AN:

67988

Other (OTH)

AF:

0.0417

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

245

490

735

980

1225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0388

Hom.:

Bravo

AF:

0.0327

Asia WGS

AF:

0.00577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism

(source)

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

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13-30467219-CTT-CT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over