NM_001128174.3:c.823-7154C>G

Variant names:

• chr4-114656841-C-G
• rs34115976
• NM_001128174.3:c.823-7154C>G

Variant summary

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

The NM_001128174.3(UGT8):​c.823-7154C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 510,638 control chromosomes in the GnomAD database, including 8,026 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 0.14 (2082 hom., cov: 32)
  • Exomes 𝑓: 0.17 (5944 hom.)
• Consequence: UGT8 NM_001128174.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 18 publications found

Genes affected

UGT8 (HGNC:12555): (UDP glycosyltransferase 8) The protein encoded by this gene belongs to the UDP-glycosyltransferase family. It catalyzes the transfer of galactose to ceramide, a key enzymatic step in the biosynthesis of galactocerebrosides, which are abundant sphingolipids of the myelin membrane of the central and peripheral nervous systems. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

MIR577 (HGNC:32833): (microRNA 577) 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128174.3. 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
	UGT8	NM_001128174.3	MANE Select	c.823-7154C>G		intron	N/A	NP_001121646.2	Q16880
	UGT8	NM_001322112.2		c.823-7154C>G		intron	N/A	NP_001309041.2	Q16880
	UGT8	NM_001322113.2		c.823-7154C>G		intron	N/A	NP_001309042.2	Q16880

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT8	ENST00000310836.11	TSL:1 MANE Select	c.823-7154C>G		intron	N/A	ENSP00000311648.6	Q16880
	UGT8	ENST00000394511.3	TSL:1	c.823-7154C>G		intron	N/A	ENSP00000378019.3	Q16880
	UGT8	ENST00000507710.2	TSL:3	c.823-7154C>G		intron	N/A	ENSP00000421446.2	Q16880

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22022 AN: 151808 Hom.: 2082 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.153

GnomAD2 exomes AF: 0.155 AC: 33785 AN: 218006 AF XY: 0.162

Gnomad AFR exome AF: 0.0446

Gnomad AMR exome AF: 0.0817

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.0524

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.184

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.172 AC: 61535 AN: 358712 Hom.: 5944 Cov.: 0 AF XY: 0.174 AC XY: 35526 AN XY: 203738

African (AFR) AF: 0.0474 AC: 475 AN: 10028

American (AMR) AF: 0.0831 AC: 2858 AN: 34384

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 2253 AN: 11096

East Asian (EAS) AF: 0.0498 AC: 639 AN: 12830

South Asian (SAS) AF: 0.161 AC: 10204 AN: 63324

European-Finnish (FIN) AF: 0.275 AC: 8521 AN: 30948

Middle Eastern (MID) AF: 0.250 AC: 653 AN: 2616

European-Non Finnish (NFE) AF: 0.187 AC: 33272 AN: 177872

Other (OTH) AF: 0.170 AC: 2660 AN: 15614

GnomAD4 genome AF: 0.145 AC: 22014 AN: 151926 Hom.: 2082 Cov.: 32 AF XY: 0.149 AC XY: 11067 AN XY: 74266

African (AFR) AF: 0.0472 AC: 1955 AN: 41458

American (AMR) AF: 0.127 AC: 1942 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3466

East Asian (EAS) AF: 0.0540 AC: 279 AN: 5164

South Asian (SAS) AF: 0.154 AC: 743 AN: 4810

European-Finnish (FIN) AF: 0.285 AC: 3015 AN: 10566

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12854 AN: 67896

Other (OTH) AF: 0.150 AC: 317 AN: 2110

Alfa AF: 0.177 Hom.: 802

Bravo AF: 0.129

Asia WGS AF: 0.100 AC: 349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.62
PhyloP100		-0.71
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: rs34115976; hg19: chr4-115577997;