rs12482676

Variant names:

• chr21-34598414-G-T
• rs12482676
• NM_004414.7:c.252+16346C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ENSG00000288711 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RCAN1	NM_004414.7	c.252+16346C>A		intron_variant	Intron 1 of 3	ENST00000313806.9	NP_004405.3
RCAN1	NM_001285389.2	c.9+15373C>A		intron_variant	Intron 1 of 3		NP_001272318.1
RCAN1	NM_203417.2	c.-154+15864C>A		intron_variant	Intron 1 of 3		NP_981962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCAN1	ENST00000313806.9	c.252+16346C>A		intron_variant	Intron 1 of 3	1	NM_004414.7	ENSP00000320768.4
ENSG00000288711	ENST00000684114.1	n.153+16346C>A		intron_variant	Intron 1 of 4			ENSP00000507841.1

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

African (AFR) AF: 0.0643 AC: 2670 AN: 41530

American (AMR) AF: 0.156 AC: 2388 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 887 AN: 3470

East Asian (EAS) AF: 0.0479 AC: 249 AN: 5194

South Asian (SAS) AF: 0.237 AC: 1145 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10590

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13444 AN: 67988

Other (OTH) AF: 0.169 AC: 357 AN: 2116

Alfa AF: 0.173 Hom.: 3401

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
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs12482676; hg19: chr21-35970712;