rs861340

Positions:

• chr4-68822246-G-A
• chr4-68822246-G-C
• chr4-68822246-G-T

Variant summary

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

The NM_001075.6(UGT2B10):​c.868-25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 1,607,622 control chromosomes in the GnomAD database, including 611,049 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.74 (45958 hom., cov: 31)
  • Exomes 𝑓: 0.88 (565091 hom.)
• Consequence: UGT2B10 NM_001075.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776

Genes affected

UGT2B10 (HGNC:12544): (UDP glucuronosyltransferase family 2 member B10) Predicted to be involved in lipid metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B10	NM_001075.6	c.868-25G>A		intron_variant		ENST00000265403.12	NP_001066.1
UGT2B10	NM_001144767.3	c.616-25G>A		intron_variant			NP_001138239.1
UGT2B10	NM_001290091.2	c.124-25G>A		intron_variant			NP_001277020.1
UGT2B10	XM_017008585.3	c.868-34G>A		intron_variant			XP_016864074.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B10	ENST00000265403.12	c.868-25G>A		intron_variant		1	NM_001075.6	ENSP00000265403.7
UGT2B10	ENST00000458688.2	c.616-25G>A		intron_variant		2		ENSP00000413420.2

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112698 AN: 151846 Hom.: 45949 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.893

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.770

GnomAD3 exomes AF: 0.845 AC: 208674 AN: 247038 Hom.: 90730 AF XY: 0.856 AC XY: 114607 AN XY: 133860

Gnomad AFR exome AF: 0.355

Gnomad AMR exome AF: 0.849

Gnomad ASJ exome AF: 0.887

Gnomad EAS exome AF: 0.686

Gnomad SAS exome AF: 0.896

Gnomad FIN exome AF: 0.929

Gnomad NFE exome AF: 0.903

Gnomad OTH exome AF: 0.875

GnomAD4 exome AF: 0.876 AC: 1275645 AN: 1455658 Hom.: 565091 Cov.: 53 AF XY: 0.879 AC XY: 636395 AN XY: 724098

Gnomad4 AFR exome AF: 0.360

Gnomad4 AMR exome AF: 0.845

Gnomad4 ASJ exome AF: 0.889

Gnomad4 EAS exome AF: 0.683

Gnomad4 SAS exome AF: 0.895

Gnomad4 FIN exome AF: 0.927

Gnomad4 NFE exome AF: 0.897

Gnomad4 OTH exome AF: 0.850

GnomAD4 genome AF: 0.742 AC: 112740 AN: 151964 Hom.: 45958 Cov.: 31 AF XY: 0.746 AC XY: 55367 AN XY: 74268

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.902

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.768

Alfa AF: 0.862 Hom.: 27841

Bravo AF: 0.713

Asia WGS AF: 0.764 AC: 2656 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.59
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs861340; hg19: chr4-69687964; COSMIC: COSV55319449;