dbSNP rs2284385: RALY:c.-10+17591A>G (chr20-34049195-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.657

Publications

10 publications found

Variant links:

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]

RALY links:

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]

MIR4755 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALY	NM_016732.3 link	c.-10+17591A>G		intron_variant	Intron 2 of 9	ENST00000246194.8	NP_057951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALY	ENST00000246194.8 link	c.-10+17591A>G		intron_variant	Intron 2 of 9	1	NM_016732.3	ENSP00000246194.3

Frequencies

GnomAD3 genomes

AF:

0.0456

AC:

6928

AN:

151766

Hom.:

228

Cov.:

show subpopulations

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:

AN:

368

AF XY:

0.0743

show subpopulations

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:

AN:

2182

Hom.:

Cov.:

AF XY:

0.0451

AC XY:

AN XY:

1086

show subpopulations

African (AFR)

AF:

0.0135

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.106

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.0380

AC:

AN:

1632

European-Non Finnish (NFE)

AF:

0.0333

AC:

AN:

180

Other (OTH)

AF:

0.0368

AC:

AN:

190

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0456

AC:

6928

AN:

151884

Hom.:

228

Cov.:

AF XY:

0.0484

AC XY:

3597

AN XY:

74246

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0578

AC:

3923

AN:

67868

Other (OTH)

AF:

0.0427

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

318

636

954

1272

1590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0544

Hom.:

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

(source)

DANN

Benign

0.59

PhyloP100

-0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over