chr20-34049195-A-G

Variant summary

Our verdict is Benign. Variant got -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

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.657
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
RALYNM_016732.3 linkuse as main transcriptc.-10+17591A>G intron_variant ENST00000246194.8
MIR4755NR_039911.1 linkuse as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RALYENST00000246194.8 linkuse as main transcriptc.-10+17591A>G intron_variant 1 NM_016732.3 P3Q9UKM9-1
MIR4755ENST00000583905.1 linkuse as main transcript downstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.0456
AC:
6928
AN:
151766
Hom.:
228
Cov.:
31
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
GnomAD3 exomes
AF:
0.0598
AC:
22
AN:
368
Hom.:
1
AF XY:
0.0743
AC XY:
15
AN XY:
202
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:
87
AN:
2182
Hom.:
4
Cov.:
0
AF XY:
0.0451
AC XY:
49
AN XY:
1086
show subpopulations
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
show subpopulations
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2284385; hg19: chr20-32637001; API