rs7850023

Variant names:

• chr9-111932206-A-G
• rs7850023
• NM_003358.3:c.861A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003358.3(UGCG):​c.861A>G​(p.Thr287Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,613,606 control chromosomes in the GnomAD database, including 64,130 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.

• Frequency:
  • Genomes: 𝑓 0.31 (7576 hom., cov: 32)
  • Exomes 𝑓: 0.27 (56554 hom.)
• Consequence: UGCG NM_003358.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 18 publications found

Genes affected

UGCG (HGNC:12524): (UDP-glucose ceramide glucosyltransferase) This gene encodes an enzyme that catalyzes the first glycosylation step in the biosynthesis of glycosphingolipids, which are membrane components containing lipid and sugar moieties. The product of this reaction is glucosylceramide, which is the core structure of many glycosphingolipids. [provided by RefSeq, Dec 2014]

MIR4668 (HGNC:41545): (microRNA 4668) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP7: Synonymous conserved (PhyloP=0.339 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003358.3. 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
	UGCG	NM_003358.3	MANE Select	c.861A>G	p.Thr287Thr	synonymous	Exon 8 of 9	NP_003349.1	Q16739
	MIR4668	NR_039814.1		n.*37A>G		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGCG	ENST00000374279.4	TSL:1 MANE Select	c.861A>G	p.Thr287Thr	synonymous	Exon 8 of 9	ENSP00000363397.3	Q16739
	UGCG	ENST00000915623.1		c.807A>G	p.Thr269Thr	synonymous	Exon 8 of 9	ENSP00000585682.1
	UGCG	ENST00000856546.1		c.861A>G	p.Thr287Thr	synonymous	Exon 8 of 9	ENSP00000526605.1

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46862 AN: 151858 Hom.: 7565 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.287

GnomAD2 exomes AF: 0.308 AC: 77356 AN: 251300 AF XY: 0.298

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.482

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.274

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.294

GnomAD4 exome AF: 0.274 AC: 400919 AN: 1461630 Hom.: 56554 Cov.: 36 AF XY: 0.273 AC XY: 198477 AN XY: 727146

African (AFR) AF: 0.360 AC: 12058 AN: 33472

American (AMR) AF: 0.467 AC: 20900 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 5826 AN: 26134

East Asian (EAS) AF: 0.236 AC: 9365 AN: 39694

South Asian (SAS) AF: 0.269 AC: 23239 AN: 86240

European-Finnish (FIN) AF: 0.316 AC: 16890 AN: 53418

Middle Eastern (MID) AF: 0.255 AC: 1472 AN: 5768

European-Non Finnish (NFE) AF: 0.265 AC: 294749 AN: 1111798

Other (OTH) AF: 0.272 AC: 16420 AN: 60388

GnomAD4 genome AF: 0.309 AC: 46926 AN: 151976 Hom.: 7576 Cov.: 32 AF XY: 0.313 AC XY: 23274 AN XY: 74278

African (AFR) AF: 0.357 AC: 14772 AN: 41434

American (AMR) AF: 0.401 AC: 6119 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 802 AN: 3468

East Asian (EAS) AF: 0.274 AC: 1417 AN: 5178

South Asian (SAS) AF: 0.267 AC: 1284 AN: 4814

European-Finnish (FIN) AF: 0.328 AC: 3467 AN: 10556

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18138 AN: 67944

Other (OTH) AF: 0.286 AC: 604 AN: 2110

Alfa AF: 0.285 Hom.: 11745

Bravo AF: 0.317

Asia WGS AF: 0.277 AC: 961 AN: 3478

EpiCase AF: 0.260

EpiControl AF: 0.260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.0
DANN	Benign	0.69
PhyloP100		0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs7850023; hg19: chr9-114694486; COSMIC: COSV65335607; COSMIC: COSV65335607;