chr20-33998942-C-T

Variant names:

• chr20-33998942-C-T
• rs6088372
• NM_016732.3:c.-93+4811C>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.-93+4811C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0851 in 151,678 control chromosomes in the GnomAD database, including 769 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 0.085 (769 hom., cov: 28)
• Consequence: RALY NM_016732.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464
• Publications: 6 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=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RALY	NM_016732.3	c.-93+4811C>T		intron_variant	Intron 1 of 9	ENST00000246194.8	NP_057951.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RALY	ENST00000246194.8	c.-93+4811C>T		intron_variant	Intron 1 of 9	1	NM_016732.3	ENSP00000246194.3

Frequencies

GnomAD3 genomes AF: 0.0852 AC: 12906 AN: 151564 Hom.: 770 Cov.: 28

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.100

Gnomad AMR AF: 0.0941

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.0778

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0634

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

GnomAD4 genome AF: 0.0851 AC: 12914 AN: 151678 Hom.: 769 Cov.: 28 AF XY: 0.0801 AC XY: 5937 AN XY: 74082

African (AFR) AF: 0.0248 AC: 1026 AN: 41356

American (AMR) AF: 0.0942 AC: 1436 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3472

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.0343 AC: 164 AN: 4784

European-Finnish (FIN) AF: 0.0778 AC: 814 AN: 10464

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9046 AN: 67894

Other (OTH) AF: 0.0627 AC: 132 AN: 2104

Alfa AF: 0.104 Hom.: 117

Bravo AF: 0.0867

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.0
DANN	Benign	0.96
PhyloP100		-0.46
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: rs6088372; hg19: chr20-32586748;