4-68822246-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001075.6(UGT2B10):​c.868-25G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
• Consequence: UGT2B10 NM_001075.6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001075.6. 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>C		intron	N/A	NP_001066.1
	UGT2B10	NM_001144767.3		c.616-25G>C		intron	N/A	NP_001138239.1
	UGT2B10	NM_001290091.2		c.124-25G>C		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>C		intron	N/A	ENSP00000265403.7
	UGT2B10	ENST00000458688.2	TSL:2	c.616-25G>C		intron	N/A	ENSP00000413420.2
	UGT2B10	ENST00000878267.1		c.868-34G>C		intron	N/A	ENSP00000548326.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.42
PhyloP100		-0.78
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;