chr13-30539242-T-G

Position:

• chr13-30539242-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001313893.1(HMGB1):​c.-14-75548A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: HMGB1 NM_001313893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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]

RBM22P2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HMGB1	NM_001313893.1	c.-14-75548A>C		intron_variant			NP_001300822.1
HMGB1	NM_001370340.1	c.-14-75548A>C		intron_variant			NP_001357269.1
RBM22P2		n.30539242T>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000405805.5	c.-14-75548A>C		intron_variant		2		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

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0495

Gnomad4 ASJ AF: 0.0530

Gnomad4 EAS AF: 0.0682

Gnomad4 SAS AF: 0.0511

Gnomad4 FIN AF: 0.0996

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.0626

Alfa AF: 0.0751 Hom.: 796

Bravo AF: 0.0535

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.32
DANN	Benign	0.26

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

Other links and lift over

dbSNP: rs11618202; hg19: chr13-31113379;