13-30459095-C-T

Variant names:

• chr13-30459095-C-T
• rs1045411
• NM_002128.7:c.*2262G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002128.7(HMGB1):​c.*2262G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,060 control chromosomes in the GnomAD database, including 3,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3754 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: HMGB1 NM_002128.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.838
• Publications: 65 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 13-30459095-C-T is Benign according to our data. Variant chr13-30459095-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250264.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	NM_002128.7	MANE Select	c.*2262G>A		3_prime_UTR	Exon 5 of 5	NP_002119.1
	HMGB1	NM_001313892.2		c.*2262G>A		3_prime_UTR	Exon 5 of 5	NP_001300821.1
	HMGB1	NM_001313893.1		c.*2262G>A		3_prime_UTR	Exon 5 of 5	NP_001300822.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000341423.10	TSL:1 MANE Select	c.*2262G>A		3_prime_UTR	Exon 5 of 5	ENSP00000345347.5
	HMGB1	ENST00000405805.5	TSL:2	c.*2262G>A		3_prime_UTR	Exon 5 of 5	ENSP00000384678.1
	ENSG00000285840	ENST00000819189.1		n.552+12799C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30699 AN: 151942 Hom.: 3749 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.256

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.178

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.202 AC: 30703 AN: 152060 Hom.: 3754 Cov.: 32 AF XY: 0.202 AC XY: 14977 AN XY: 74302

African (AFR) AF: 0.0761 AC: 3159 AN: 41520

American (AMR) AF: 0.168 AC: 2570 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1108 AN: 5176

South Asian (SAS) AF: 0.139 AC: 669 AN: 4818

European-Finnish (FIN) AF: 0.358 AC: 3766 AN: 10526

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18146 AN: 67962

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.239 Hom.: 11780

Bravo AF: 0.182

Asia WGS AF: 0.209 AC: 729 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28423715)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.075
DANN	Benign	0.53
PhyloP100		-0.84
Mutation Taster		=100/0	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: rs1045411; hg19: chr13-31033232;