rs4353357

Positions:

• chr13-30474506-G-A
• chr13-30474506-G-C

Variant summary

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

The ENST00000648233.2(ENSG00000285840):​n.300+4896G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,154 control chromosomes in the GnomAD database, including 3,733 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 0.22 (3733 hom., cov: 32)
• Consequence: ENST00000648233.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_001313893.1	c.-14-10812C>T		intron_variant
HMGB1	NM_001370340.1	c.-14-10812C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000648233.2	n.300+4896G>A		intron_variant, non_coding_transcript_variant
HMGB1	ENST00000405805.5	c.-14-10812C>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33450 AN: 152036 Hom.: 3732 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.220 AC: 33456 AN: 152154 Hom.: 3733 Cov.: 32 AF XY: 0.220 AC XY: 16378 AN XY: 74382

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.212

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.247

Alfa AF: 0.230 Hom.: 5802

Bravo AF: 0.220

Asia WGS AF: 0.241 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.67

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: rs4353357; hg19: chr13-31048643;