rs2284385

Positions:

• chr20-34049195-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016732.3(RALY):​c.-10+17591A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0455 in 154,066 control chromosomes in the GnomAD database, including 232 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 0.046 (228 hom., cov: 31)
  • Exomes 𝑓: 0.040 (4 hom.)
• Consequence: RALY NM_016732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.657

Genes affected

RALY (HGNC:15921): (RALY heterogeneous nuclear ribonucleoprotein) This gene encodes a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) gene family. This protein may play a role in pre-mRNA splicing and in embryonic development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

MIR4755 (HGNC:41815): (microRNA 4755) 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 (SAS) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RALY	NM_016732.3	c.-10+17591A>G		intron_variant		ENST00000246194.8
MIR4755	NR_039911.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RALY	ENST00000246194.8	c.-10+17591A>G		intron_variant		1	NM_016732.3	P3
MIR4755	ENST00000583905.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0456 AC: 6928 AN: 151766 Hom.: 228 Cov.: 31

Gnomad AFR AF: 0.00894

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0645

Gnomad EAS AF: 0.0943

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.0844

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0578

Gnomad OTH AF: 0.0427

GnomAD3 exomes AF: 0.0598 AC: 22 AN: 368 Hom.: 1 AF XY: 0.0743 AC XY: 15 AN XY: 202

Gnomad AFR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad NFE exome AF: 0.0571

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.0399 AC: 87 AN: 2182 Hom.: 4 Cov.: 0 AF XY: 0.0451 AC XY: 49 AN XY: 1086

Gnomad4 AFR exome AF: 0.0135

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.106

Gnomad4 NFE exome AF: 0.0333

Gnomad4 OTH exome AF: 0.0368

GnomAD4 genome AF: 0.0456 AC: 6928 AN: 151884 Hom.: 228 Cov.: 31 AF XY: 0.0484 AC XY: 3597 AN XY: 74246

Gnomad4 AFR AF: 0.00892

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.0645

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.0844

Gnomad4 NFE AF: 0.0578

Gnomad4 OTH AF: 0.0427

Alfa AF: 0.0553 Hom.: 51

Bravo AF: 0.0378

Asia WGS AF: 0.0770 AC: 266 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	3.7
DANN	Benign	0.59

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: rs2284385; hg19: chr20-32637001;