7-34941031-T-C

Variant names:

• chr7-34941031-T-C
• rs1649215
• NM_001366673.1:c.1690-704A>G

Variant summary

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

The NM_001366673.1(DPY19L1):​c.1690-704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,844 control chromosomes in the GnomAD database, including 5,773 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 0.27 (5773 hom., cov: 31)
• Consequence: DPY19L1 NM_001366673.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 3 publications found

Genes affected

DPY19L1 (HGNC:22205): (dpy-19 like C-mannosyltransferase 1) Predicted to enable mannosyltransferase activity. Predicted to be involved in protein C-linked glycosylation via 2'-alpha-mannosyl-L-tryptophan. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000294671 (HGNC:):

MIR548N (HGNC:35330): (microRNA 548n) 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DPY19L1	NM_001366673.1	c.1690-704A>G		intron_variant	Intron 18 of 21	ENST00000638088.2	NP_001353602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DPY19L1	ENST00000638088.2	c.1690-704A>G		intron_variant	Intron 18 of 21	5	NM_001366673.1	ENSP00000490722.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40947 AN: 151726 Hom.: 5764 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.295

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 40978 AN: 151844 Hom.: 5773 Cov.: 31 AF XY: 0.267 AC XY: 19781 AN XY: 74190

African (AFR) AF: 0.187 AC: 7742 AN: 41486

American (AMR) AF: 0.263 AC: 4020 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1240 AN: 3466

East Asian (EAS) AF: 0.136 AC: 700 AN: 5130

South Asian (SAS) AF: 0.215 AC: 1036 AN: 4816

European-Finnish (FIN) AF: 0.313 AC: 3298 AN: 10522

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21993 AN: 67854

Other (OTH) AF: 0.292 AC: 616 AN: 2106

Alfa AF: 0.161 Hom.: 333

Bravo AF: 0.264

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.53
DANN	Benign	0.63
PhyloP100		-1.1
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: rs1649215; hg19: chr7-34980643;