11-32091344-C-G

Variant names:

• chr11-32091344-C-G
• rs895173058
• NM_002901.4:c.148C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002901.4(RCN1):​c.148C>G​(p.Pro50Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,548,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P50S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: RCN1 NM_002901.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08302292).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002901.4. 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
	RCN1	NM_002901.4	MANE Select	c.148C>G	p.Pro50Ala	missense	Exon 1 of 6	NP_002892.1	Q15293-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCN1	ENST00000054950.4	TSL:1 MANE Select	c.148C>G	p.Pro50Ala	missense	Exon 1 of 6	ENSP00000054950.4	Q15293-1
	ENSG00000285283	ENST00000532942.5	TSL:2	c.102-5800C>G		intron	N/A	ENSP00000436422.1
	RCN1	ENST00000972102.1		c.148C>G	p.Pro50Ala	missense	Exon 1 of 6	ENSP00000642161.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000130 AC: 2 AN: 154398 AF XY: 0.0000122

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000340

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000179 AC: 25 AN: 1396550 Hom.: 0 Cov.: 32 AF XY: 0.0000189 AC XY: 13 AN XY: 688850

African (AFR) AF: 0.00 AC: 0 AN: 31464

American (AMR) AF: 0.00 AC: 0 AN: 35656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25138

East Asian (EAS) AF: 0.00 AC: 0 AN: 35706

South Asian (SAS) AF: 0.00 AC: 0 AN: 79076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4988

European-Non Finnish (NFE) AF: 0.0000232 AC: 25 AN: 1078344

Other (OTH) AF: 0.00 AC: 0 AN: 57846

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152178 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74336

African (AFR) AF: 0.0000241 AC: 1 AN: 41454

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.53
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.64	T
M_CAP	Pathogenic	0.39	D
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		2.0
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.038
Sift	Benign	0.79	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.090
MVP		0.28
MPC		0.46
ClinPred		0.039	T
GERP RS		1.5
PromoterAI		0.027	Neutral
Varity_R		0.092
gMVP		0.48
Mutation Taster		=94/6	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: rs895173058; hg19: chr11-32112890;