20-34057745-C-T

Variant names:

• chr20-34057745-C-T
• rs8119937
• NM_016732.3:c.-9-14321C>T

Variant summary

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

The NM_016732.3(RALY):​c.-9-14321C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,140 control chromosomes in the GnomAD database, including 30,725 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 0.63 (30725 hom., cov: 29)
• Consequence: RALY NM_016732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860
• Publications: 14 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALY	NM_016732.3	c.-9-14321C>T		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	c.-9-14321C>T		intron_variant	Intron 2 of 9	1	NM_016732.3	ENSP00000246194.3

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94437 AN: 151044 Hom.: 30716 Cov.: 29

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.598

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.851

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.669

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

GnomAD4 genome AF: 0.625 AC: 94479 AN: 151140 Hom.: 30725 Cov.: 29 AF XY: 0.638 AC XY: 47057 AN XY: 73814

African (AFR) AF: 0.434 AC: 17823 AN: 41024

American (AMR) AF: 0.660 AC: 10007 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2682 AN: 3468

East Asian (EAS) AF: 0.829 AC: 4231 AN: 5104

South Asian (SAS) AF: 0.851 AC: 4097 AN: 4814

European-Finnish (FIN) AF: 0.751 AC: 7787 AN: 10370

Middle Eastern (MID) AF: 0.786 AC: 228 AN: 290

European-Non Finnish (NFE) AF: 0.673 AC: 45674 AN: 67904

Other (OTH) AF: 0.671 AC: 1406 AN: 2094

Alfa AF: 0.653 Hom.: 17066

Bravo AF: 0.606

Asia WGS AF: 0.786 AC: 2733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.53
PhyloP100		0.086
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: rs8119937; hg19: chr20-32645551;