4-114656841-C-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT8	NM_001128174.3	c.823-7154C>G		intron_variant	Intron 2 of 5	ENST00000310836.11	NP_001121646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT8	ENST00000310836.11	c.823-7154C>G		intron_variant	Intron 2 of 5	1	NM_001128174.3	ENSP00000311648.6
UGT8	ENST00000394511.3	c.823-7154C>G		intron_variant	Intron 1 of 4	1		ENSP00000378019.3
MIR577	ENST00000385196.1	n.83C>G		non_coding_transcript_exon_variant	Exon 1 of 1	6

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

GnomAD3 exomes AF: 0.155 AC: 33785 AN: 218006 Hom.: 3024 AF XY: 0.162 AC XY: 18967 AN XY: 117136

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 SAS exome AF: 0.159

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

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.0831

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.0498

Gnomad4 SAS exome AF: 0.161

Gnomad4 FIN exome AF: 0.275

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.170

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

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0540

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.150

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs34115976; hg19: chr4-115577997;