6-46461928-C-T

Variant names:

• chr6-46461928-C-T
• rs9381454
• NM_001251974.2:c.-2-4950G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001251974.2(RCAN2):​c.-2-4950G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,014 control chromosomes in the GnomAD database, including 17,586 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 0.47 (17586 hom., cov: 33)
• Consequence: RCAN2 NM_001251974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 3 publications found

Genes affected

RCAN2 (HGNC:3041): (regulator of calcineurin 2) This gene encodes a member of the regulator of calcineurin (RCAN) protein family. These proteins play a role in many physiological processes by binding to the catalytic domain of calcineurin A, inhibiting calcineurin-mediated nuclear translocation of the transcription factor NFATC1. Expression of this gene in skin fibroblasts is upregulated by thyroid hormone, and the encoded protein may also play a role in endothelial cell function and angiogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCAN2	NM_001251974.2	c.-2-4950G>A		intron_variant	Intron 1 of 4	ENST00000371374.6	NP_001238903.1
RCAN2	NM_001251973.2	c.-2-4950G>A		intron_variant	Intron 1 of 4		NP_001238902.1
RCAN2	XM_011514226.2	c.-2-4950G>A		intron_variant	Intron 1 of 4		XP_011512528.1
RCAN2	XM_024446301.2	c.-2-4950G>A		intron_variant	Intron 1 of 4		XP_024302069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCAN2	ENST00000371374.6	c.-2-4950G>A		intron_variant	Intron 1 of 4	1	NM_001251974.2	ENSP00000360425.1
RCAN2	ENST00000306764.11	c.-2-4950G>A		intron_variant	Intron 1 of 4	1		ENSP00000305223.7

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71640 AN: 151896 Hom.: 17563 Cov.: 33

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.472 AC: 71713 AN: 152014 Hom.: 17586 Cov.: 33 AF XY: 0.475 AC XY: 35292 AN XY: 74268

African (AFR) AF: 0.348 AC: 14448 AN: 41466

American (AMR) AF: 0.480 AC: 7328 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3464

East Asian (EAS) AF: 0.604 AC: 3119 AN: 5164

South Asian (SAS) AF: 0.406 AC: 1954 AN: 4818

European-Finnish (FIN) AF: 0.633 AC: 6680 AN: 10550

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.518 AC: 35222 AN: 67980

Other (OTH) AF: 0.471 AC: 990 AN: 2104

Alfa AF: 0.497 Hom.: 18469

Bravo AF: 0.458

Asia WGS AF: 0.505 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.37
DANN	Benign	0.48
PhyloP100		-1.1
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: rs9381454; hg19: chr6-46429665;