20-34057246-T-C

Variant names:

• chr20-34057246-T-C
• rs6059651
• NM_016732.3:c.-9-14820T>C

Variant summary

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

The NM_016732.3(RALY):​c.-9-14820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,182 control chromosomes in the GnomAD database, including 42,421 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 0.74 (42421 hom., cov: 32)
• Consequence: RALY NM_016732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALY	NM_016732.3	c.-9-14820T>C		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.-9-14820T>C		intron_variant	Intron 2 of 9	1	NM_016732.3	ENSP00000246194.3

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112903 AN: 152064 Hom.: 42378 Cov.: 32

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.828

Gnomad SAS AF: 0.853

Gnomad FIN AF: 0.748

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.743 AC: 112997 AN: 152182 Hom.: 42421 Cov.: 32 AF XY: 0.750 AC XY: 55795 AN XY: 74380

African (AFR) AF: 0.840 AC: 34905 AN: 41530

American (AMR) AF: 0.710 AC: 10865 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2699 AN: 3468

East Asian (EAS) AF: 0.829 AC: 4295 AN: 5184

South Asian (SAS) AF: 0.852 AC: 4109 AN: 4820

European-Finnish (FIN) AF: 0.748 AC: 7912 AN: 10572

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45827 AN: 67988

Other (OTH) AF: 0.758 AC: 1603 AN: 2114

Alfa AF: 0.695 Hom.: 18557

Bravo AF: 0.742

Asia WGS AF: 0.807 AC: 2808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.82
DANN	Benign	0.58
PhyloP100		-1.3
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: rs6059651; hg19: chr20-32645052;