chr13-30467219-CT-C

Variant names:

• chr13-30467219-CT-C
• rs41369348
• NM_001313893.1:c.-14-3526delA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001313893.1(HMGB1):​c.-14-3526delA variant causes a intron 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: HMGB1 NM_001313893.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ENSG00000285840 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4927 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HMGB1	NM_001313893.1	c.-14-3526delA		intron_variant	Intron 1 of 4		NP_001300822.1
HMGB1	NM_001370340.1	c.-14-3526delA		intron_variant	Intron 1 of 4		NP_001357269.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGB1	ENST00000405805.5	c.-14-3526delA		intron_variant	Intron 1 of 4	2		ENSP00000384678.1
ENSG00000285840	ENST00000648233.2	n.176+928delT		intron_variant	Intron 1 of 3
ENSG00000285840	ENST00000819189.1	n.553-14025delT		intron_variant	Intron 1 of 1
ENSG00000285840	ENST00000819190.1	n.504-13210delT		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.00826 AC: 343 AN: 41502

American (AMR) AF: 0.0354 AC: 541 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0952 AC: 330 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0116 AC: 56 AN: 4820

European-Finnish (FIN) AF: 0.0179 AC: 190 AN: 10598

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0486 AC: 3301 AN: 67988

Other (OTH) AF: 0.0417 AC: 88 AN: 2108

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

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism

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: rs41369348; hg19: chr13-31041356;