13-30467219-CTT-CT

Position:

• chr13-30467219-CTT-CT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000648233.2(ENSG00000285840):​n.176+935del 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 0.0324 in 152,146 control chromosomes in the GnomAD database, including 126 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.032 (126 hom., cov: 32)
• Consequence: ENST00000648233.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0324 (4927/152146) while in subpopulation NFE AF= 0.0486 (3301/67988). AF 95% confidence interval is 0.0472. There are 126 homozygotes in gnomad4. There are 2278 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 126 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HMGB1	NM_001313893.1	c.-14-3526del		intron_variant
HMGB1	NM_001370340.1	c.-14-3526del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000648233.2	n.176+935del		intron_variant, non_coding_transcript_variant
HMGB1	ENST00000405805.5	c.-14-3526del		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4931 AN: 152028 Hom.: 126 Cov.: 32

Gnomad AFR AF: 0.00831

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0952

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0179

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.0422

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

GnomAD4 genome AF: 0.0324 AC: 4927 AN: 152146 Hom.: 126 Cov.: 32 AF XY: 0.0306 AC XY: 2278 AN XY: 74390

Gnomad4 AFR AF: 0.00826

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0952

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0116

Gnomad4 FIN AF: 0.0179

Gnomad4 NFE AF: 0.0486

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0388 Hom.: 24

Bravo AF: 0.0327

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs41369348; hg19: chr13-31041356;