chr4-68822246-G-A

Variant names:

• chr4-68822246-G-A
• rs861340
• NM_001075.6:c.868-25G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265403.12(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 ENST00000265403.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.776
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265403.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B10	NM_001075.6	MANE Select	c.868-25G>A		intron	N/A	NP_001066.1
	UGT2B10	NM_001144767.3		c.616-25G>A		intron	N/A	NP_001138239.1
	UGT2B10	NM_001290091.2		c.124-25G>A		intron	N/A	NP_001277020.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B10	ENST00000265403.12	TSL:1 MANE Select	c.868-25G>A		intron	N/A	ENSP00000265403.7
	UGT2B10	ENST00000458688.2	TSL:2	c.616-25G>A		intron	N/A	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

GnomAD2 exomes AF: 0.845 AC: 208674 AN: 247038 AF XY: 0.856

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 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

African (AFR) AF: 0.360 AC: 11888 AN: 33054

American (AMR) AF: 0.845 AC: 36650 AN: 43360

Ashkenazi Jewish (ASJ) AF: 0.889 AC: 23143 AN: 26020

East Asian (EAS) AF: 0.683 AC: 27037 AN: 39596

South Asian (SAS) AF: 0.895 AC: 76220 AN: 85196

European-Finnish (FIN) AF: 0.927 AC: 49517 AN: 53398

Middle Eastern (MID) AF: 0.901 AC: 3836 AN: 4258

European-Non Finnish (NFE) AF: 0.897 AC: 996350 AN: 1110750

Other (OTH) AF: 0.850 AC: 51004 AN: 60026

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

African (AFR) AF: 0.374 AC: 15480 AN: 41384

American (AMR) AF: 0.818 AC: 12465 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3126 AN: 3466

East Asian (EAS) AF: 0.689 AC: 3545 AN: 5148

South Asian (SAS) AF: 0.893 AC: 4301 AN: 4816

European-Finnish (FIN) AF: 0.929 AC: 9854 AN: 10608

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61248 AN: 67990

Other (OTH) AF: 0.768 AC: 1623 AN: 2112

Alfa AF: 0.830 Hom.: 41381

Bravo AF: 0.713

Asia WGS AF: 0.764 AC: 2656 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		-0.78
BranchPoint Hunter		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs861340; hg19: chr4-69687964; COSMIC: COSV55319449;