rs2300390

Variant names:

• chr21-34597217-A-G
• rs2300390
• NM_004414.7:c.252+17543T>C

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+17543T>C 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 152,198 control chromosomes in the GnomAD database, including 2,088 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 (2088 hom., cov: 32)
• Consequence: RCAN1 NM_004414.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.283
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCAN1	NM_004414.7	c.252+17543T>C		intron_variant	Intron 1 of 3	ENST00000313806.9	NP_004405.3
RCAN1	NM_001285389.2	c.9+16570T>C		intron_variant	Intron 1 of 3		NP_001272318.1
RCAN1	NM_203417.2	c.-154+17061T>C		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+17543T>C		intron_variant	Intron 1 of 3	1	NM_004414.7	ENSP00000320768.4
ENSG00000288711	ENST00000684114.1	n.153+17543T>C		intron_variant	Intron 1 of 4			ENSP00000507841.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22878 AN: 152080 Hom.: 2086 Cov.: 32

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.0497

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.199

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: 22877 AN: 152198 Hom.: 2088 Cov.: 32 AF XY: 0.150 AC XY: 11179 AN XY: 74410

African (AFR) AF: 0.0640 AC: 2657 AN: 41522

American (AMR) AF: 0.157 AC: 2404 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 886 AN: 3468

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5184

South Asian (SAS) AF: 0.242 AC: 1166 AN: 4820

European-Finnish (FIN) AF: 0.131 AC: 1389 AN: 10600

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13468 AN: 68002

Other (OTH) AF: 0.169 AC: 356 AN: 2106

Alfa AF: 0.186 Hom.: 3714

Bravo AF: 0.146

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.7
DANN	Benign	0.68
PhyloP100		0.28
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: rs2300390; hg19: chr21-35969515; COSMIC: COSV58252284;