Variant 13-30461464-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1BP4_StrongBP6_Very_StrongBS2

The NM_002128.7(HMGB1):c.541A>G(p.Ser181Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,559,298 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

HMGB1
NM_002128.7 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.87

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM1

In a mutagenesis_site Cytoplasmic localization (phosphorylation mimicking); when associated with E-35; E-39; E-42; E-46 and E-53. (size 0) in uniprot entity HMGB1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.0064373314).

BP6

Variant 13-30461464-T-C is Benign according to our data. Variant chr13-30461464-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 710363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 314 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGB1	NM_002128.7 linkuse as main transcript	c.541A>G	p.Ser181Gly	missense_variant	5/5	ENST00000341423.10	NP_002119.1	P09429A0A024RDR0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000341423.10 linkuse as main transcript	c.541A>G	p.Ser181Gly	missense_variant	5/5	1	NM_002128.7	ENSP00000345347.5		P09429

Frequencies

GnomAD3 genomes

AF:

0.00206

AC:

314

AN:

152066

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00263

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00189

AC:

308

AN:

162744

Hom.:

AF XY:

0.00203

AC XY:

176

AN XY:

86552

show subpopulations

Gnomad AFR exome

AF:

0.000434

Gnomad AMR exome

AF:

0.00306

Gnomad ASJ exome

AF:

0.000228

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00263

Gnomad FIN exome

AF:

0.000315

Gnomad NFE exome

AF:

0.00234

Gnomad OTH exome

AF:

0.00240

GnomAD4 exome

AF:

0.00197

AC:

2767

AN:

1407114

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1424

AN XY:

695628

show subpopulations

Gnomad4 AFR exome

AF:

0.000314

Gnomad4 AMR exome

AF:

0.00252

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000265

Gnomad4 SAS exome

AF:

0.00254

Gnomad4 FIN exome

AF:

0.000303

Gnomad4 NFE exome

AF:

0.00214

Gnomad4 OTH exome

AF:

0.00179

GnomAD4 genome

AF:

0.00206

AC:

314

AN:

152184

Hom.:

Cov.:

AF XY:

0.00207

AC XY:

154

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00641

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00263

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00183

Hom.:

Bravo

AF:

0.00205

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000606

AC:

ExAC

AF:

0.00119

AC:

137

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;T;T;T

Eigen

Benign

-0.0067

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.76

.;.;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.0064

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.4

M;M;M;M

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0080

D;D;D;D

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.015

B;B;B;B

Vest4

0.29

MVP

0.51

MPC

.;4.45352357014E-4;.;.

ClinPred

0.023

GERP RS

5.7

Varity_R

0.18

gMVP

0.047

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over