NM_004414.7:c.252+10920A>G

Variant names:

• chr21-34603840-T-C
• rs7277304
• NM_004414.7:c.252+10920A>G

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+10920A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 152,094 control chromosomes in the GnomAD database, including 34,545 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 0.67 (34545 hom., cov: 32)
• Consequence: RCAN1 NM_004414.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004414.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCAN1	NM_004414.7	MANE Select	c.252+10920A>G		intron	N/A	NP_004405.3
	RCAN1	NM_001285389.2		c.9+9947A>G		intron	N/A	NP_001272318.1	P53805-3
	RCAN1	NM_203417.2		c.-154+10438A>G		intron	N/A	NP_981962.1	P53805-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCAN1	ENST00000313806.9	TSL:1 MANE Select	c.252+10920A>G		intron	N/A	ENSP00000320768.4	P53805-1
	RCAN1	ENST00000399272.5	TSL:1	c.9+9947A>G		intron	N/A	ENSP00000382214.1	P53805-3
	RCAN1	ENST00000443408.6	TSL:1	c.-154+10438A>G		intron	N/A	ENSP00000392438.2	P53805-4

Frequencies

GnomAD3 genomes AF: 0.665 AC: 101125 AN: 151978 Hom.: 34541 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.744

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.664

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

GnomAD4 genome AF: 0.665 AC: 101166 AN: 152094 Hom.: 34545 Cov.: 32 AF XY: 0.670 AC XY: 49843 AN XY: 74346

African (AFR) AF: 0.506 AC: 20975 AN: 41482

American (AMR) AF: 0.744 AC: 11372 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.679 AC: 2356 AN: 3472

East Asian (EAS) AF: 0.916 AC: 4740 AN: 5174

South Asian (SAS) AF: 0.747 AC: 3595 AN: 4810

European-Finnish (FIN) AF: 0.708 AC: 7492 AN: 10582

Middle Eastern (MID) AF: 0.678 AC: 198 AN: 292

European-Non Finnish (NFE) AF: 0.711 AC: 48337 AN: 67972

Other (OTH) AF: 0.665 AC: 1401 AN: 2106

Alfa AF: 0.691 Hom.: 8890

Bravo AF: 0.664

Asia WGS AF: 0.769 AC: 2674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.71
PhyloP100		0.47
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: rs7277304; hg19: chr21-35976138;