rs6025590

Variant names:

• chr20-57495449-A-G
• rs6025590
• ENST00000522557.2:c.-1124T>C

Your query was ambiguous. Multiple possible variants found:

• chr20-57495449-A-G
• chr20-57495449-A-T

Variant summary

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

The ENST00000522557.2(HMGB1P1):​c.-1124T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 152,144 control chromosomes in the GnomAD database, including 37,667 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 0.70 (37667 hom., cov: 33)
• Consequence: HMGB1P1 ENST00000522557.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.28

Genes affected

HMGB1P1 (HGNC:4993): (high mobility group box 1 pseudogene 1) This gene may represent an evolving retropseudogene of the high-mobility group box 1 gene, which has multiple pseudogenes. This gene has an intact open reading frame, where the length of encoded protein is conserved, compared to the high-mobility group box 1 protein. However, due to the lack of conclusive evidence for specific transcription at this location, this locus is currently represented as a pseudogene. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HMGB1P1	ENST00000522557.2	c.-1124T>C		upstream_gene_variant		6		ENSP00000508468.1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105621 AN: 152026 Hom.: 37593 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.670

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.620

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.695 AC: 105756 AN: 152144 Hom.: 37667 Cov.: 33 AF XY: 0.694 AC XY: 51643 AN XY: 74376

Gnomad4 AFR AF: 0.860

Gnomad4 AMR AF: 0.670

Gnomad4 ASJ AF: 0.582

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.620

Gnomad4 OTH AF: 0.658

Alfa AF: 0.632 Hom.: 63642

Bravo AF: 0.703

Asia WGS AF: 0.734 AC: 2552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6025590; hg19: chr20-56070505;