rs12845504

Variant names:

• chrX-17828632-C-T
• rs12845504
• NM_021785.6:c.-24-26598G>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.-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
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAI2	NM_021785.6	c.-24-26598G>A		intron_variant	Intron 1 of 1	ENST00000451717.6	NP_068557.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAI2	ENST00000451717.6	c.-24-26598G>A		intron_variant	Intron 1 of 1	1	NM_021785.6	ENSP00000401323.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 15885 AN: 111367 Hom.: 1144 Cov.: 22

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

African (AFR) AF: 0.0371 AC: 1139 AN: 30711

American (AMR) AF: 0.107 AC: 1127 AN: 10549

Ashkenazi Jewish (ASJ) AF: 0.271 AC: 715 AN: 2641

East Asian (EAS) AF: 0.0169 AC: 60 AN: 3540

South Asian (SAS) AF: 0.120 AC: 317 AN: 2651

European-Finnish (FIN) AF: 0.180 AC: 1075 AN: 5957

Middle Eastern (MID) AF: 0.294 AC: 63 AN: 214

European-Non Finnish (NFE) AF: 0.206 AC: 10929 AN: 52968

Other (OTH) AF: 0.157 AC: 239 AN: 1518

Alfa AF: 0.174 Hom.: 6167

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
PhyloP100		0.26
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: rs12845504; hg19: chrX-17846752;