rs7277304

chr21-34603840-T-Cchr21-34603840-T-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RCAN1	NM_004414.7	c.252+10920A>G		intron_variant		ENST00000313806.9
RCAN1	NM_001285389.2	c.9+9947A>G		intron_variant
RCAN1	NM_203417.2	c.-154+10438A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RCAN1	ENST00000313806.9	c.252+10920A>G		intron_variant		1	NM_004414.7

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

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.744

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.747

Gnomad4 FIN AF: 0.708

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.665

Alfa AF: 0.694 Hom.: 8767

Bravo AF: 0.664

Asia WGS AF: 0.769 AC: 2674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.2
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7277304; hg19: chr21-35976138;