NM_021785.6:c.-25+24926G>A

Variant names:

• chrX-17836172-C-T
• rs10521677
• NM_021785.6:c.-25+24926G>A

Variant summary

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

The NM_021785.6(RAI2):​c.-25+24926G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 110,387 control chromosomes in the GnomAD database, including 88 homozygotes. There are 1,192 hemizygotes in GnomAD. 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 0.038 (88 hom., 1192 hem., cov: 23)
• Consequence: RAI2 NM_021785.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 0 publications found

Genes affected

RAI2 (HGNC:9835): (retinoic acid induced 2) Retinoic acid plays a critical role in development, cellular growth, and differentiation. The specific function of this retinoic acid-induced gene has not yet been determined but it may play a role in development. The chromosomal location of this gene designates it to be a candidate for diseases such as Nance-Horan syndrome, sensorineural deafness, non-specific X-linked cognitive disability, oral-facial-digital syndrome, and Fried syndrome. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

RAI2 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0568 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021785.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI2	NM_021785.6	MANE Select	c.-25+24926G>A		intron	N/A	NP_068557.4	Q9Y5P3-1
	RAI2	NM_001172739.2		c.-25+1365G>A		intron	N/A	NP_001166210.2	Q9Y5P3-1
	RAI2	NM_001172743.2		c.-25+1365G>A		intron	N/A	NP_001166214.2	Q9Y5P3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAI2	ENST00000451717.6	TSL:1 MANE Select	c.-25+24926G>A		intron	N/A	ENSP00000401323.1	Q9Y5P3-1
	RAI2	ENST00000360011.5	TSL:1	c.-25+1365G>A		intron	N/A	ENSP00000353106.1	Q9Y5P3-1
	RAI2	ENST00000331511.5	TSL:2	c.-25+1365G>A		intron	N/A	ENSP00000333456.1	Q9Y5P3-1

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 4210 AN: 110334 Hom.: 89 Cov.: 23

Gnomad AFR AF: 0.00703

Gnomad AMI AF: 0.0743

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000286

Gnomad SAS AF: 0.0659

Gnomad FIN AF: 0.0537

Gnomad MID AF: 0.0386

Gnomad NFE AF: 0.0585

Gnomad OTH AF: 0.0302

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

GnomAD4 genome AF: 0.0381 AC: 4204 AN: 110387 Hom.: 88 Cov.: 23 AF XY: 0.0364 AC XY: 1192 AN XY: 32733

African (AFR) AF: 0.00701 AC: 213 AN: 30379

American (AMR) AF: 0.0219 AC: 227 AN: 10378

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 98 AN: 2637

East Asian (EAS) AF: 0.000287 AC: 1 AN: 3481

South Asian (SAS) AF: 0.0645 AC: 164 AN: 2541

European-Finnish (FIN) AF: 0.0537 AC: 308 AN: 5735

Middle Eastern (MID) AF: 0.0374 AC: 8 AN: 214

European-Non Finnish (NFE) AF: 0.0585 AC: 3090 AN: 52842

Other (OTH) AF: 0.0299 AC: 45 AN: 1507

Alfa AF: 0.0470 Hom.: 288

Bravo AF: 0.0324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.27
DANN	Benign	0.51
PhyloP100		-0.096
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: rs10521677; hg19: chrX-17854292;