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. The variant received -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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000522557.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HMGB1P1	ENST00000522557.2	TSL:6	c.-1124T>C		upstream_gene	N/A	ENSP00000508468.1	B2RPK0

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

African (AFR) AF: 0.860 AC: 35704 AN: 41536

American (AMR) AF: 0.670 AC: 10240 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2018 AN: 3466

East Asian (EAS) AF: 0.655 AC: 3390 AN: 5176

South Asian (SAS) AF: 0.746 AC: 3599 AN: 4826

European-Finnish (FIN) AF: 0.616 AC: 6514 AN: 10580

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.620 AC: 42154 AN: 67964

Other (OTH) AF: 0.658 AC: 1389 AN: 2112

Alfa AF: 0.645 Hom.: 143526

Bravo AF: 0.703

Asia WGS AF: 0.734 AC: 2552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.21
PhyloP100		-6.3
PromoterAI		0.012	Neutral

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6025590;

hg19: chr20-56070505;