rs12482676

Positions:

• chr21-34598414-G-T

Variant summary

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

The NM_004414.7(RCAN1):​c.252+16346C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,188 control chromosomes in the GnomAD database, including 2,077 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 0.15 (2077 hom., cov: 33)
• Consequence: RCAN1 NM_004414.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848

Genes affected

RCAN1 (HGNC:3040): (regulator of calcineurin 1) The protein encoded by this gene interacts with calcineurin A and inhibits calcineurin-dependent signaling pathways, possibly affecting central nervous system development. This gene is located in the minimal candidate region for the Down syndrome phenotype, and is overexpressed in the brain of Down syndrome fetuses. Chronic overexpression of this gene may lead to neurofibrillary tangles such as those associated with Alzheimer disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCAN1	NM_004414.7	c.252+16346C>A		intron_variant		ENST00000313806.9	NP_004405.3
RCAN1	NM_001285389.2	c.9+15373C>A		intron_variant			NP_001272318.1
RCAN1	NM_203417.2	c.-154+15864C>A		intron_variant			NP_981962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCAN1	ENST00000313806.9	c.252+16346C>A		intron_variant		1	NM_004414.7	ENSP00000320768

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22813 AN: 152070 Hom.: 2075 Cov.: 33

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.0476

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.150 AC: 22812 AN: 152188 Hom.: 2077 Cov.: 33 AF XY: 0.150 AC XY: 11135 AN XY: 74412

Gnomad4 AFR AF: 0.0643

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.0479

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.169

Alfa AF: 0.153 Hom.: 443

Bravo AF: 0.146

Asia WGS AF: 0.141 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.87
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs12482676; hg19: chr21-35970712;