chr13-30539242-T-G

Variant names:

• chr13-30539242-T-G
• rs11618202

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The variant allele was found at a frequency of 0.0583 in 152,286 control chromosomes in the GnomAD database, including 349 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.058 (349 hom., cov: 32)
• Consequence: RBM22P2 intragenic
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 6 publications found

Genes affected

RBM22P2 (HGNC:39695): (RNA binding motif protein 22 pseudogene 2)

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000405805.5. 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_001313893.1		c.-14-75548A>C		intron	N/A	NP_001300822.1
	HMGB1	NM_001370340.1		c.-14-75548A>C		intron	N/A	NP_001357269.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1	ENST00000405805.5	TSL:2	c.-14-75548A>C		intron	N/A	ENSP00000384678.1

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 8862 AN: 152168 Hom.: 346 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.0530

Gnomad EAS AF: 0.0681

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0996

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.0570

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

GnomAD4 genome AF: 0.0583 AC: 8878 AN: 152286 Hom.: 349 Cov.: 32 AF XY: 0.0582 AC XY: 4332 AN XY: 74466

African (AFR) AF: 0.0158 AC: 655 AN: 41562

American (AMR) AF: 0.0495 AC: 757 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 184 AN: 3470

East Asian (EAS) AF: 0.0682 AC: 354 AN: 5188

South Asian (SAS) AF: 0.0511 AC: 247 AN: 4830

European-Finnish (FIN) AF: 0.0996 AC: 1057 AN: 10608

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0795 AC: 5408 AN: 68022

Other (OTH) AF: 0.0626 AC: 132 AN: 2108

Alfa AF: 0.0707 Hom.: 1110

Bravo AF: 0.0535

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.32
DANN	Benign	0.26
PhyloP100		-1.8
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: rs11618202; hg19: chr13-31113379;