chr20-34049195-A-G

Variant names:

• chr20-34049195-A-G
• rs2284385
• NM_016732.3:c.-10+17591A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016732.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALY	NM_016732.3	MANE Select	c.-10+17591A>G		intron	N/A	NP_057951.1
	RALY	NM_007367.4		c.-10+17591A>G		intron	N/A	NP_031393.2
	MIR4755	NR_039911.1		n.*5A>G		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALY	ENST00000246194.8	TSL:1 MANE Select	c.-10+17591A>G		intron	N/A	ENSP00000246194.3
	RALY	ENST00000375114.7	TSL:1	c.-10+17591A>G		intron	N/A	ENSP00000364255.3
	RALY	ENST00000442805.1	TSL:5	c.-10+17591A>G		intron	N/A	ENSP00000415973.1

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

GnomAD2 exomes AF: 0.0598 AC: 22 AN: 368 AF XY: 0.0743

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

African (AFR) AF: 0.0135 AC: 1 AN: 74

American (AMR) AF: 0.125 AC: 1 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.106 AC: 10 AN: 94

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.0380 AC: 62 AN: 1632

European-Non Finnish (NFE) AF: 0.0333 AC: 6 AN: 180

Other (OTH) AF: 0.0368 AC: 7 AN: 190

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

African (AFR) AF: 0.00892 AC: 370 AN: 41492

American (AMR) AF: 0.0274 AC: 419 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0645 AC: 224 AN: 3472

East Asian (EAS) AF: 0.0945 AC: 480 AN: 5080

South Asian (SAS) AF: 0.0956 AC: 460 AN: 4812

European-Finnish (FIN) AF: 0.0844 AC: 891 AN: 10554

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0578 AC: 3923 AN: 67868

Other (OTH) AF: 0.0427 AC: 90 AN: 2108

Alfa AF: 0.0544 Hom.: 51

Bravo AF: 0.0378

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		-0.66
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: rs2284385; hg19: chr20-32637001;