rs12845504

Positions:

• chrX-17828632-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021785.6(RAI2):​c.-24-26598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 111,424 control chromosomes in the GnomAD database, including 1,143 homozygotes. There are 4,568 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 0.14 (1143 hom., 4568 hem., cov: 22)
• Consequence: RAI2 NM_021785.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.262

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAI2	NM_021785.6	c.-24-26598G>A		intron_variant		ENST00000451717.6	NP_068557.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAI2	ENST00000451717.6	c.-24-26598G>A		intron_variant		1	NM_021785.6	ENSP00000401323	P1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15885 AN: 111367 Hom.: 1144 Cov.: 22 AF XY: 0.136 AC XY: 4561 AN XY: 33601

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0169

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.295

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.143 AC: 15887 AN: 111424 Hom.: 1143 Cov.: 22 AF XY: 0.136 AC XY: 4568 AN XY: 33668

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.0169

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.206

Gnomad4 OTH AF: 0.157

Alfa AF: 0.185 Hom.: 4123

Bravo AF: 0.133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.61
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs12845504; hg19: chrX-17846752;