NM_002128.7:c.309C>T

Variant names:

• chr13-30462700-G-A
• rs1060348
• NM_002128.7:c.309C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002128.7(HMGB1):​c.309C>T​(p.Phe103Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.0356 in 1,607,636 control chromosomes in the GnomAD database, including 2,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.082 (1160 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1529 hom.)
• Consequence: HMGB1 NM_002128.7 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.61
• Publications: 13 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 13-30462700-G-A is Benign according to our data. Variant chr13-30462700-G-A is described in ClinVar as Benign. ClinVar VariationId is 3055268.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

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.309C>T	p.Phe103Phe	synonymous	Exon 4 of 5	NP_002119.1	P09429
	HMGB1	NM_001313892.2		c.309C>T	p.Phe103Phe	synonymous	Exon 4 of 5	NP_001300821.1	P09429
	HMGB1	NM_001313893.1		c.309C>T	p.Phe103Phe	synonymous	Exon 4 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.309C>T	p.Phe103Phe	synonymous	Exon 4 of 5	ENSP00000345347.5	P09429
	HMGB1	ENST00000399489.5	TSL:1	c.309C>T	p.Phe103Phe	synonymous	Exon 3 of 5	ENSP00000382412.1	Q5T7C4
	HMGB1	ENST00000927783.1		c.309C>T	p.Phe103Phe	synonymous	Exon 4 of 5	ENSP00000597842.1

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 12499 AN: 151964 Hom.: 1158 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0197

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0714

GnomAD2 exomes AF: 0.0350 AC: 8626 AN: 246658 AF XY: 0.0314

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.0254

Gnomad ASJ exome AF: 0.0328

Gnomad EAS exome AF: 0.000822

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.0248

Gnomad OTH exome AF: 0.0342

GnomAD4 exome AF: 0.0307 AC: 44619 AN: 1455554 Hom.: 1529 Cov.: 32 AF XY: 0.0297 AC XY: 21535 AN XY: 724028

African (AFR) AF: 0.239 AC: 7865 AN: 32908

American (AMR) AF: 0.0267 AC: 1161 AN: 43428

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 827 AN: 25882

East Asian (EAS) AF: 0.000403 AC: 16 AN: 39668

South Asian (SAS) AF: 0.0179 AC: 1513 AN: 84754

European-Finnish (FIN) AF: 0.0130 AC: 695 AN: 53380

Middle Eastern (MID) AF: 0.0535 AC: 307 AN: 5734

European-Non Finnish (NFE) AF: 0.0269 AC: 29852 AN: 1109712

Other (OTH) AF: 0.0397 AC: 2383 AN: 60088

GnomAD4 genome AF: 0.0824 AC: 12533 AN: 152082 Hom.: 1160 Cov.: 32 AF XY: 0.0801 AC XY: 5951 AN XY: 74336

African (AFR) AF: 0.233 AC: 9644 AN: 41438

American (AMR) AF: 0.0385 AC: 589 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3472

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4826

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10580

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0259 AC: 1762 AN: 67976

Other (OTH) AF: 0.0730 AC: 154 AN: 2110

Alfa AF: 0.0436 Hom.: 303

Bravo AF: 0.0917

Asia WGS AF: 0.0320 AC: 111 AN: 3478

EpiCase AF: 0.0284

EpiControl AF: 0.0268

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	HMGB1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		5.6
Mutation Taster		=84/16	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: rs1060348; hg19: chr13-31036837;