rs28575804

Variant names:

• chr4-69391612-A-G
• rs28575804

Your query was ambiguous. Multiple possible variants found:

• chr4-69391612-A-G
• chr4-69391612-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PVS1_Moderate BS2

The ENST00000511504.2(UGT2B25P):​n.868+1A>G variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.156 in 1,385,200 control chromosomes in the GnomAD database, including 28,290 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.17 (2197 hom., cov: 29)
  • Exomes 𝑓: 0.16 (26093 hom.)
• Consequence: UGT2B25P ENST00000511504.2 splice_donor, intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 5.53
• Publications: 3 publications found

Genes affected

UGT2B25P (HGNC:12549): (UDP glucuronosyltransferase family 2 member B25, pseudogene)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene. Cryptic splice site detected, with MaxEntScore 8.1, offset of 0 (no position change), new splice context is: aagGTaaac. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
• BS2: High Homozygotes in GnomAd4 at 2197 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511504.2. 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
	UGT2B25P	ENST00000511504.2	TSL:6	n.868+1A>G		splice_donor intron	N/A

Frequencies

GnomAD3 genomes AF: 0.166 AC: 24367 AN: 146486 Hom.: 2193 Cov.: 29

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.0909

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.155 AC: 192217 AN: 1238606 Hom.: 26093 Cov.: 33 AF XY: 0.157 AC XY: 97405 AN XY: 618826

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.140 AC: 3624 AN: 25946

American (AMR) AF: 0.101 AC: 2940 AN: 29008

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2351 AN: 23442

East Asian (EAS) AF: 0.0991 AC: 3472 AN: 35050

South Asian (SAS) AF: 0.159 AC: 11164 AN: 70064

European-Finnish (FIN) AF: 0.184 AC: 9537 AN: 51692

Middle Eastern (MID) AF: 0.128 AC: 686 AN: 5340

European-Non Finnish (NFE) AF: 0.159 AC: 150665 AN: 945432

Other (OTH) AF: 0.148 AC: 7778 AN: 52632

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.166 AC: 24386 AN: 146594 Hom.: 2197 Cov.: 29 AF XY: 0.163 AC XY: 11621 AN XY: 71486

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.161 AC: 6403 AN: 39794

American (AMR) AF: 0.122 AC: 1800 AN: 14762

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 370 AN: 3398

East Asian (EAS) AF: 0.116 AC: 581 AN: 5028

South Asian (SAS) AF: 0.155 AC: 724 AN: 4664

European-Finnish (FIN) AF: 0.166 AC: 1665 AN: 10058

Middle Eastern (MID) AF: 0.0986 AC: 28 AN: 284

European-Non Finnish (NFE) AF: 0.189 AC: 12393 AN: 65670

Other (OTH) AF: 0.126 AC: 260 AN: 2058

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0731 Hom.: 87

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Keratoconus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.85
PhyloP100		5.5

Splicing

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

Other links and lift over

dbSNP: rs28575804; hg19: chr4-70257330; COSMIC: COSV72665166;