rs1171559344

Variant names:

• chr13-30463266-G-A
• rs1171559344
• NM_002128.7:c.237C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002128.7(HMGB1):​c.237C>T​(p.Ile79Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000871 in 1,607,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: HMGB1 NM_002128.7 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.256
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 13-30463266-G-A is Benign according to our data. Variant chr13-30463266-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 747322.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.256 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 13 AD gene.

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.237C>T	p.Ile79Ile	synonymous	Exon 3 of 5	NP_002119.1	P09429
	HMGB1	NM_001313892.2		c.237C>T	p.Ile79Ile	synonymous	Exon 3 of 5	NP_001300821.1	P09429
	HMGB1	NM_001313893.1		c.237C>T	p.Ile79Ile	synonymous	Exon 3 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.237C>T	p.Ile79Ile	synonymous	Exon 3 of 5	ENSP00000345347.5	P09429
	HMGB1	ENST00000399489.5	TSL:1	c.237C>T	p.Ile79Ile	synonymous	Exon 2 of 5	ENSP00000382412.1	Q5T7C4
	HMGB1	ENST00000927783.1		c.237C>T	p.Ile79Ile	synonymous	Exon 3 of 5	ENSP00000597842.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000162 AC: 4 AN: 247270 AF XY: 0.0000299

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000903

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.00000893 AC: 13 AN: 1455182 Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8 AN XY: 723932

African (AFR) AF: 0.00 AC: 0 AN: 32894

American (AMR) AF: 0.0000693 AC: 3 AN: 43304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26056

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 85010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4158

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110700

Other (OTH) AF: 0.0000833 AC: 5 AN: 60030

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152222 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

African (AFR) AF: 0.00 AC: 0 AN: 41462

American (AMR) AF: 0.0000655 AC: 1 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.7
DANN	Benign	0.78
PhyloP100		-0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1171559344; hg19: chr13-31037403; COSMIC: COSV58104394; COSMIC: COSV58104394;