4-69489575-GA-GAAAAAAA

Variant names:

• chr4-69489575-G-GAAAAAA
• rs199604241
• NM_021139.3:c.871-11_871-6dupTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021139.3(UGT2B4):​c.871-11_871-6dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGT2B4 NM_021139.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

Genes affected

UGT2B4 (HGNC:12553): (UDP glucuronosyltransferase family 2 member B4) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation and estrogen 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B4	NM_021139.3	c.871-11_871-6dupTTTTTT		splice_region_variant, intron_variant	Intron 2 of 5	ENST00000305107.7	NP_066962.2
UGT2B4	NM_001297616.2	c.463-11_463-6dupTTTTTT		splice_region_variant, intron_variant	Intron 3 of 6		NP_001284545.1
UGT2B4	NM_001297615.2	c.871-11_871-6dupTTTTTT		splice_region_variant, intron_variant	Intron 2 of 4		NP_001284544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B4	ENST00000305107.7	c.871-6_871-5insTTTTTT		splice_region_variant, intron_variant	Intron 2 of 5	1	NM_021139.3	ENSP00000305221.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs199604241; hg19: chr4-70355293;