20-34000289-T-C

Variant names:

• chr20-34000289-T-C
• rs2284378
• NM_016732.3:c.-93+6158T>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.-93+6158T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,788 control chromosomes in the GnomAD database, including 42,201 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 (42201 hom., cov: 28)
• Consequence: RALY NM_016732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 85 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.832 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.-93+6158T>C		intron	N/A	NP_057951.1
	RALY	NM_007367.4		c.-93+6158T>C		intron	N/A	NP_031393.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RALY	ENST00000246194.8	TSL:1 MANE Select	c.-93+6158T>C		intron	N/A	ENSP00000246194.3
	RALY	ENST00000375114.7	TSL:1	c.-93+6158T>C		intron	N/A	ENSP00000364255.3
	RALY	ENST00000874581.1		c.-93+6158T>C		intron	N/A	ENSP00000544640.1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112478 AN: 151670 Hom.: 42164 Cov.: 28

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.832

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.673

Gnomad OTH AF: 0.755

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

GnomAD4 genome AF: 0.742 AC: 112565 AN: 151788 Hom.: 42201 Cov.: 28 AF XY: 0.749 AC XY: 55575 AN XY: 74184

African (AFR) AF: 0.840 AC: 34734 AN: 41368

American (AMR) AF: 0.709 AC: 10830 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2672 AN: 3470

East Asian (EAS) AF: 0.833 AC: 4291 AN: 5154

South Asian (SAS) AF: 0.852 AC: 4073 AN: 4782

European-Finnish (FIN) AF: 0.749 AC: 7883 AN: 10524

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.673 AC: 45706 AN: 67904

Other (OTH) AF: 0.756 AC: 1599 AN: 2114

Alfa AF: 0.698 Hom.: 82943

Bravo AF: 0.741

Asia WGS AF: 0.809 AC: 2814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.72
DANN	Benign	0.74
PhyloP100		-1.8
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: rs2284378; hg19: chr20-32588095;