11-32097148-A-G

Variant names:

• chr11-32097148-A-G
• rs199769797
• NM_002901.4:c.259A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_002901.4(RCN1):​c.259A>G​(p.Ile87Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000294 in 1,497,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00030 (0 hom.)
• Consequence: RCN1 NM_002901.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.28
• Publications: 1 publications found

Genes affected

RCN1 (HGNC:9934): (reticulocalbin 1) Reticulocalbin 1 is a calcium-binding protein located in the lumen of the ER. The protein contains six conserved regions with similarity to a high affinity Ca(+2)-binding motif, the EF-hand. High conservation of amino acid residues outside of these motifs, in comparison to mouse reticulocalbin, is consistent with a possible biochemical function besides that of calcium binding. In human endothelial and prostate cancer cell lines this protein localizes to the plasma membrane.[provided by RefSeq, Jan 2009]

ENSG00000285283 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15509331).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCN1	NM_002901.4	c.259A>G	p.Ile87Val	missense_variant	Exon 2 of 6	ENST00000054950.4	NP_002892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCN1	ENST00000054950.4	c.259A>G	p.Ile87Val	missense_variant	Exon 2 of 6	1	NM_002901.4	ENSP00000054950.4
ENSG00000285283	ENST00000532942.5	c.106A>G	p.Ile36Val	missense_variant	Exon 2 of 6	2		ENSP00000436422.1

Frequencies

GnomAD3 genomes AF: 0.000262 AC: 39 AN: 148734 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000997

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000201

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000474

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000206 AC: 31 AN: 150436 AF XY: 0.000177

Gnomad AFR exome AF: 0.000146

Gnomad AMR exome AF: 0.000124

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000358

Gnomad OTH exome AF: 0.000288

GnomAD4 exome AF: 0.000297 AC: 401 AN: 1348252 Hom.: 0 Cov.: 34 AF XY: 0.000294 AC XY: 195 AN XY: 662256

African (AFR) AF: 0.000102 AC: 3 AN: 29526

American (AMR) AF: 0.000200 AC: 5 AN: 24962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20338

East Asian (EAS) AF: 0.00 AC: 0 AN: 37364

South Asian (SAS) AF: 0.00 AC: 0 AN: 65322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49116

Middle Eastern (MID) AF: 0.000190 AC: 1 AN: 5258

European-Non Finnish (NFE) AF: 0.000357 AC: 379 AN: 1060960

Other (OTH) AF: 0.000235 AC: 13 AN: 55406

GnomAD4 genome AF: 0.000262 AC: 39 AN: 148826 Hom.: 0 Cov.: 30 AF XY: 0.000249 AC XY: 18 AN XY: 72302

African (AFR) AF: 0.0000994 AC: 4 AN: 40226

American (AMR) AF: 0.000201 AC: 3 AN: 14926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5116

South Asian (SAS) AF: 0.00 AC: 0 AN: 4690

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.000474 AC: 32 AN: 67458

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.000236 Hom.: 0

Bravo AF: 0.000283

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000157 AC: 19

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.259A>G (p.I87V) alteration is located in exon 2 (coding exon 2) of the RCN1 gene. This alteration results from a A to G substitution at nucleotide position 259, causing the isoleucine (I) at amino acid position 87 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.68
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Pathogenic	3.2	.;M
PhyloP100		9.3
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.87	N;N
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.33	.;B
Vest4		0.43
MVP		0.74
MPC		0.59
ClinPred		0.12	T
GERP RS		5.0
Varity_R		0.41
gMVP		0.42
Mutation Taster		=52/48	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs199769797; hg19: chr11-32118694;